Sticky signaling - Adhesion class g protein-coupled receptors take the stage

Science Signaling

Volumn 6, Issue 276, 2013, Pages

  Langenhan, Tobias ^a   Aust, Gabriela ^b   Hamann, Jörg ^c  

^a UNIVERSITY OF WÜRZBURG   (Germany)

^b UNIVERSITY OF LEIPZIG   (Germany)

^c UNIVERSITY OF AMSTERDAM   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

G PROTEIN COUPLED RECEPTOR; GUANOSINE TRIPHOSPHATASE; MEMBRANE PROTEIN;

CELL ADHESION; HUMAN; IMMUNE RESPONSE; INTRACELLULAR SIGNALING; MOSAICISM; NONHUMAN; OLIGOMERIZATION; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; REVIEW; TUMOR GROWTH;

ANIMALS; BIOLOGICAL EVOLUTION; HUMANS; LIGANDS; PROTEIN BINDING; PROTEOLYSIS; RECEPTORS, G-PROTEIN-COUPLED; SIGNAL TRANSDUCTION;

EID: 84878318013     PISSN: 19450877     EISSN: 19379145     Source Type: Journal    
DOI: 10.1126/scisignal.2003825     Document Type: Review

References (216)

1. K. L. Pierce, R. T. Premont, R. J. Lefkowitz, Seven-transmembrane receptors. Nat. Rev. Mol. Cell Biol. 3, 639-650 (2002).
2. R. Fredriksson, M. C. Lagerström, L. G. Lundin, H. B. Schiöth, The G-protein-coupled receptors in the human genome form five main families. Phylogenetic analysis, paralogon groups, and fingerprints. Mol. Pharmacol. 63, 1256-1272 (2003).
3. M. C. Lagerström, H. B. Schiöth, Structural diversity of G protein-coupled receptors and significance for drug discovery. Nat. Rev. Drug Discov. 7, 339-357 (2008).
4. T. K. Bjarnadóttir, R. Fredriksson, P. J. Höglund, D. E. Gloriam, M. C. Lagerström, H. B. Schiöth, The human and mouse repertoire of the adhesion family of G-protein-coupled receptors. Genomics 84, 23-33 (2004).
5. S. Gordon, J. Hamann, H. H. Lin, M. Stacey, F4/80 and the related adhesion-GPCRs. Eur. J. Immunol. 41, 2472-2476 (2011).
6. V. Baud, S. L. Chissoe, E. Viegas-Péquignot, S. Diriong, V. C. N'Guyen, B. A. Roe, M. Lipinski, EMR1, an unusual member in the family of hormone receptors with seven transmembrane segments. Genomics 26, 334-344 (1995).
7. J. Hamann, W. Eichler, D. Hamann, H. M. Kerstens, P. J. Poddighe, J. M. Hoovers, E. Hartmann, M. Strauss, R. A. van Lier, Expression cloning and chromosomal mapping of the leukocyte activation antigen CD97, a new seven-span transmembrane molecule of the secretion receptor superfamily with an unusual extracellular domain. J. Immunol. 155, 1942-1950 (1995).
8. J. X. Gray, M. Haino, M. J. Roth, J. E. Maguire, P. N. Jensen, A. Yarme, M. A. Stetler- Stevenson, U. Siebenlist, K. Kelly, CD97 is a processed, seven-transmembrane, heterodimeric receptor associated with inflammation. J. Immunol. 157, 5438-5447 (1996).
9. A. J. McKnight, A. J. Macfarlane, P. Dri, L. Turley, A. C. Willis, S. Gordon, Molecular cloning of F4/80, a murine macrophage-restricted cell surface glycoprotein with homology to the G-protein-linked transmembrane 7 hormone receptor family. J. Biol. Chem. 271, 486-489 (1996).
10. M. J. Kwakkenbos, E. N. Kop, M. Stacey, M. Matmati, S. Gordon, H. H. Lin, J. Hamann, The EGF-TM7 family: A postgenomic view. Immunogenetics 55, 655-666 (2004).
11. V. G. Krasnoperov, M. A. Bittner, R. Beavis, Y. Kuang, K. V. Salnikow, O. G. Chepurny, A. R. Little, A. N. Plotnikov, D. Wu, R. W. Holz, A. G. Petrenko, a-Latrotoxin stimulates exocytosis by the interaction with a neuronal G-protein-coupled receptor. Neuron 18, 925-937 (1997).
12. V. G. Lelianova, B. A. Davletov, A. Sterling, M. A. Rahman, E. V. Grishin, N. F. Totty, Y. A. Ushkaryov, a-Latrotoxin receptor, latrophilin, is a novel member of the secretin family of G protein-coupled receptors. J. Biol. Chem. 272, 21504-21508 (1997).
13. J. Hamann, E. Hartmann, R. A. van Lier, Structure of the human CD97 gene: Exon shuffling has generated a new type of seven-span transmembrane molecule related to the secretin receptor superfamily. Genomics 32, 144-147 (1996).
14. M. Stacey, H. H. Lin, S. Gordon, A. J. McKnight, LNB-TM7, a group of seven-transmembrane proteins related to family-B G-protein-coupled receptors. Trends Biochem. Sci. 25, 284-289 (2000).
15. A. J. Harmar, Family-B G-protein-coupled receptors. Genome Biol. 2, REVIEWS3013 (2001).
16. S. Yona, H. H. Lin, W. O. Siu, S. Gordon, M. Stacey, Adhesion-GPCRs: Emerging roles for novel receptors. Trends Biochem. Sci. 33, 491-500 (2008).
17. A. Krishnan, M. S. Almén, R. Fredriksson, H. B. Schiöth, The origin of GPCRs: Identification of mammalian like Rhodopsin, Adhesion, Glutamate and Frizzled GPCRs in fungi. PLoS One 7, e29817 (2012).
18. K. J. V. Nordström, M. C. Lagerström, L. M. J. Wallér, R. Fredriksson, H. B. Schiöth, The Secretin GPCRs descended from the family of Adhesion GPCRs. Mol. Biol. Evol. 26, 71-84 (2009).
19. M. J. Kwakkenbos, M. Matmati, O. Madsen, W. Pouwels, Y. Wang, R. E. Bontrop, P. J. Heidt, R. M. Hoek, J. Hamann, An unusual mode of concerted evolution of the EGF-TM7 receptor chimera EMR2. FASEB J. 20, 2582-2584 (2006).
20. X. Piao, R. S. Hill, A. Bodell, B. S. Chang, L. Basel-Vanagaite, R. Straussberg, W. B. Dobyns, B. Qasrawi, R. M.Winter, A. M. Innes, T. Voit, M. E. Ross, J. L. Michaud, J. C. Déscarie, A. J. Barkovich, C. A. Walsh, G protein-coupled receptor-dependent development of human frontal cortex. Science 303, 2033-2036 (2004).
21. T. Usui, Y. Shima, Y. Shimada, S. Hirano, R. W. Burgess, T. L. Schwarz, M. Takeichi, T. Uemura, Flamingo, a seven-pass transmembrane cadherin, regulates planar cell polarity under the control of Frizzled. Cell 98, 585-595 (1999).
22. F. Tissir, I. Bar, Y. Jossin, O. De Backer, A. M. Goffinet, Protocadherin Celsr3 is crucial in axonal tract development. Nat. Neurosci. 8, 451-457 (2005).
23. J. Reiners, E. vanWijk, T. Märker, U. Zimmermann, K. Jürgens, H. te Brinke, N. Overlack, R. Roepman, M. Knipper, H. Kremer, U. Wolfrum, Scaffold protein harmonin (USH1C) provides molecular links between Usher syndrome type 1 and type 2. Hum. Mol. Genet. 14, 3933-3943 (2005).
24. J. McGee, R. J. Goodyear, D. R. McMillan, E. A. Stauffer, J. R. Holt, K. G. Locke, D. G. Birch, P. K. Legan, P. C. White, E. J. Walsh, G. P. Richardson, The very large G-protein-coupled receptor VLGR1: A component of the ankle link complex required for the normal development of auditory hair bundles. J. Neurosci. 26, 6543-6553 (2006).
25. T. Langenhan, S. Prömel, L. Mestek, B. Esmaeili, H.Waller-Evans, C. Hennig, Y. Kohara, L. Avery, I. Vakonakis, R. Schnabel, A. P. Russ, Latrophilin signaling links anterior-posterior tissue polarity and oriented cell divisions in the C. elegans embryo. Dev. Cell 17, 494-504 (2009).
26. T. Nishimura, H. Honda, M. Takeichi, Planar cell polarity links axes of spatial dynamics in neural-tube closure. Cell 149, 1084-1097 (2012).
27. C. Boutin, A. M. Goffinet, F. Tissir, Celsr1-3 cadherins in PCP and brain development. Curr. Top. Dev. Biol. 101, 161-183 (2012).
28. F. B. Gao, J. E. Brenman, L. Y. Jan, Y. N. Jan, Genes regulating dendritic outgrowth, branching, and routing in Drosophila. Genes Dev. 13, 2549-2561 (1999).
29. E. N. Kop, M. J. Kwakkenbos, G. J. D. Teske, M. C. Kraan, T. J. Smeets, M. Stacey, H. H. Lin, P. P. Tak, J. Hamann, Identification of the epidermal growth factor-TM7 receptor EMR2 and its ligand dermatan sulfate in rheumatoid synovial tissue. Arthritis Rheum. 52, 442-450 (2005).
30. L. Xu, S. Begum, J. D. Hearn, R. O. Hynes, GPR56, an atypical G protein-coupled receptor, binds tissue transglutaminase, TG2, and inhibits melanoma tumor growth and metastasis. Proc. Natl. Acad. Sci. U.S.A. 103, 9023-9028 (2006).
31. S. Yona, H. H. Lin, P. Dri, J. Q. Davies, R. P. G. Hayhoe, S. M. Lewis, S. E. M. Heinsbroek, K. A. Brown, M. Perretti, J. Hamann, D. F. Treacher, S. Gordon, M. Stacey, Ligation of the adhesion-GPCR EMR2 regulates human neutrophil function. FASEB J. 22, 741-751 (2008).
32. S. Koirala, Z. Jin, X. Piao, G. Corfas, GPR56-regulated granule cell adhesion is essential for rostral cerebellar development. J. Neurosci. 29, 7439-7449 (2009).
33. A. Steimel, L. Wong, E. H. Najarro, B. D. Ackley, G. Garriga, H. Hutter, The Flamingo ortholog FMI-1 controls pioneer-dependent navigation of follower axons in C. elegans. Development 137, 3663-3673 (2010).
34. Y. M. Peng, M. D. B. van de Garde, K. F. Cheng, P. A. Baars, E. B. M. Remmerswaal, R. A. W. van Lier, C. R. Mackay, H. H. Lin, J. Hamann, Specific expression of GPR56 by human cytotoxic lymphocytes. J. Leukoc. Biol. 90, 735-740 (2011).
35. E. H. Najarro, L. Wong, M. Zhen, E. P. Carpio, A. Goncharov, G. Garriga, E. A. Lundquist, Y. Jin, B. D. Ackley, Caenorhabditis elegans flamingo cadherin fmi-1 regulates GABAergic neuronal development. J. Neurosci. 32, 4196-4211 (2012).
36. V. Krasnoperov, Y. Lu, L. Buryanovsky, T. A. Neubert, K. Ichtchenko, A. G. Petrenko, Post-translational proteolytic processing of the calcium-independent receptor of a-latrotoxin (CIRL), a natural chimera of the cell adhesion protein and the G protein-coupled receptor. Role of the G protein-coupled receptor proteolysis site (GPS) motif. J. Biol. Chem. 277, 46518-46526 (2002).
37. H. H. Lin, G. W. Chang, J. Q. Davies, M. Stacey, J. Harris, S. Gordon, Autocatalytic cleavage of the EMR2 receptor occurs at a conserved G protein-coupled receptor proteolytic site motif. J. Biol. Chem. 279, 31823-31832 (2004).
38. D. Araç, A. A. Boucard, M. F. Bolliger, J. Nguyen, S. M. Soltis, T. C. Südhof, A. T. Brunger, A novel evolutionarily conserved domain of cell-adhesion GPCRs mediates autoproteolysis. EMBO J. 31, 1364-1378 (2012).
39. D. R. McMillan, K. M. Kayes-Wandover, J. A. Richardson, P. C. White, Very large G protein-coupled receptor-1, the largest known cell surface protein, is highly expressed in the developing central nervous system. J. Biol. Chem. 277, 785-792 (2002).
40. R. F. Doolittle, The multiplicity of domains in proteins. Annu. Rev. Biochem. 64, 287-314 (1995).
41. I. Vakonakis, T. Langenhan, S. Prömel, A. Russ, I. D. Campbell, Solution structure and sugar-binding mechanism of mouse latrophilin-1 RBL: A 7TM receptor-attached lectin-like domain. Structure 16, 944-953 (2008).
42. B. Kaur, D. J. Brat, N. S. Devi, E. G. Van Meir, Vasculostatin, a proteolytic fragment of brain angiogenesis inhibitor 1, is an antiangiogenic and antitumorigenic factor. Oncogene 24, 3632-3642 (2005).
43. D. R. McMillan, P. C. White, in Adhesion-GPCRs, S. Yona, M. Stacey, Eds. (Landes Bioscience, Austin, TX, 2010).
44. J. Hamann, B. Vogel, G. M. van Schijndel, R. A. van Lier, The seven-span transmembrane receptor CD97 has a cellular ligand (CD55, DAF). J. Exp. Med. 184, 1185-1189 (1996).
45. M. Stacey, G. W. Chang, J. Q. Davies, M. J. Kwakkenbos, R. D. Sanderson, J. Hamann, S. Gordon, H. H. Lin, The epidermal growth factor-like domains of the human EMR2 receptor mediate cell attachment through chondroitin sulfate glycosaminoglycans. Blood 102, 2916-2924 (2003).
46. J. Hamann, C. Stortelers, E. Kiss-Toth, B. Vogel, W. Eichler, R. A. van Lier, Characterization of the CD55 (DAF)-binding site on the seven-span transmembrane receptor CD97. Eur. J. Immunol. 28, 1701-1707 (1998).
47. H. H. Lin, M. Stacey, C. Saxby, V. Knott, Y. Chaudhry, D. Evans, S. Gordon, A. J. McKnight, P. Handford, S. Lea, Molecular analysis of the epidermal growth factor-like short consensus repeat domain-mediated protein-protein interactions: Dissection of the CD97-CD55 complex. J. Biol. Chem. 276, 24160-24169 (2001).
48. M. Wobus, B. Vogel, E. Schmücking, J. Hamann, G. Aust, N-glycosylation of CD97 within the EGF domains is crucial for epitope accessibility in normal and malignant cells as well as CD55 ligand binding. Int. J. Cancer 112, 815-822 (2004).
49. M. J. Kwakkenbos, W. Pouwels, M. Matmati, M. Stacey, H. H. Lin, S. Gordon, R. A. W. van Lier, J. Hamann, Expression of the largest CD97 and EMR2 isoforms on leukocytes facilitates a specific interaction with chondroitin sulfate on B cells. J. Leukoc. Biol. 77, 112-119 (2005).
50. H. H. Lin, M. Stacey, J. Hamann, S. Gordon, A. J. McKnight, Human EMR2, a novel EGF-TM7 molecule on chromosome 19p13.1, is closely related to CD97. Genomics 67, 188-200 (2000).
51. A. A. Boucard, J. Ko, T. C. Südhof, High affinity neurexin binding to cell adhesion G-protein-coupled receptor CIRL1/latrophilin-1 produces an intercellular adhesion complex. J. Biol. Chem. 287, 9399-9413 (2012).
52. S.Das, K. A. Owen, K. T. Ly, D. Park, S. G. Black, J.M.Wilson,C.D. Sifri, K. S. Ravichandran, P. B. Ernst, J. E. Casanova, Brain angiogenesis inhibitor 1 (BAI1) is a pattern recognition receptor that mediates macrophage binding and engulfment of Gram-negative bacteria. Proc. Natl. Acad. Sci. U.S.A. 108, 2136-2141 (2011).
53. M. F. Bolliger, D. C. Martinelli, T. C. Südhof, The cell-adhesion G protein-coupled receptor BAI3 is a high-affinity receptor for C1q-like proteins. Proc. Natl. Acad. Sci. U.S.A. 108, 2534-2539 (2011).
54. R. Luo, Z. Jin, Y. Deng, N. Strokes, X. Piao, Disease-associated mutations prevent GPR56-collagen III interaction. PLoS One 7, e29818 (2012).
55. V. Krasnoperov, M. A. Bittner, R. W. Holz, O. Chepurny, A. G. Petrenko, Structural requirements for α-latrotoxin binding and α-latrotoxin- stimulated secretion. A study with calcium-independent receptor of α-latrotoxin (CIRL) deletion mutants. J. Biol. Chem. 274, 3590-3596 (1999).
56. E. Wandel, A. Saalbach, D. Sittig, C. Gebhardt, G. Aust, Thy-1 (CD90) is an interacting partner for CD97 on activated endothelial cells. J. Immunol. 188, 1442-1450 (2012).
57. J. P. Silva, V. G. Lelianova, Y. S. Ermolyuk, N. Vysokov, P. G. Hitchen, O. Berninghausen, M. A. Rahman, A. Zangrandi, S. Fidalgo, A. G. Tonevitsky, A. Dell, K. E. Volynski, Y. A. Ushkaryov, Latrophilin 1 and its endogenous ligand Lasso/teneurin-2 form a high-affinity transsynaptic receptor pair with signaling capabilities. Proc. Natl. Acad. Sci. U.S.A. 108, 12113-12118 (2011).
58. Y. Shima, M. Kengaku, T. Hirano, M. Takeichi, T. Uemura, Regulation of dendritic maintenance and growth by a mammalian 7-pass transmembrane cadherin. Dev. Cell 7, 205-216 (2004).
59. W. S. Chen, D. Antic, M. Matis, C. Y. Logan, M. Povelones, G. A. Anderson, R. Nusse, J. D. Axelrod, Asymmetric homotypic interactions of the atypical cadherin flamingo mediate intercellular polarity signaling. Cell 133, 1093-1105 (2008).
60. K. J. Paavola, J. R. Stephenson, S. L. Ritter, S. P. Alter, R. A. Hall, The N terminus of the adhesion G protein-coupled receptor GPR56 controls receptor signaling activity. J. Biol. Chem. 286, 28914-28921 (2011).
61. D. Park, A. C. Tosello-Trampont, M. R. Elliott, M. Lu, L. B. Haney, Z. Ma, A. L. Klibanov, J. W. Mandell, K. S. Ravichandran, BAI1 is an engulfment receptor for apoptotic cells upstream of the ELMO/Dock180/Rac module. Nature 450, 430-434 (2007).
62. R. Luo, S. J. Jeong, Z. Jin, N. Strokes, S. Li, X. Piao, G protein-coupled receptor 56 and collagen III, a receptor-ligand pair, regulates cortical development and lamination. Proc. Natl. Acad. Sci. U.S.A. 108, 12925-12930 (2011).
63. G. Parsonage, A. D. Filer, O. Haworth, G. B. Nash, G. E. Rainger, M. Salmon, C. D. Buckley, A stromal address code defined by fibroblasts. Trends Immunol. 26, 150-156 (2005).
64. H. Veninga, R. M. Hoek, A. F. de Vos, A. M. de Bruin, F. Q. An, T. van der Poll, R. A. W. van Lier, M. E. Medof, J. Hamann, A novel role for CD55 in granulocyte homeostasis and anti-bacterial host defense. PLoS One 6, e24431 (2011).
65. R. M. Hoek, D. de Launay, E. N. Kop, A. S. Yilmaz-Elis, F. Lin, K. A. Reedquist, J. S. Verbeek, M. E. Medof, P. P. Tak, J. Hamann, Deletion of either CD55 or CD97 ameliorates arthritis in mouse models. Arthritis Rheum. 62, 1036-1042 (2010).
66. X. Piao, B. S. Chang, A. Bodell, K. Woods, B. Benzeev, M. Topcu, R. Guerrini, H. Goldberg-Stern, L. Sztriha, W. B. Dobyns, A. J. Barkovich, C. A. Walsh, Genotype-phenotype analysis of human frontoparietal polymicrogyria syndromes. Ann. Neurol. 58, 680-687 (2005).
67. N. Y. Chiang, C. C. Hsiao, Y. S. Huang, H. Y. Chen, I. J. Hsieh, G. W. Chang, H. H. Lin, Disease-associated GPR56 mutations cause bilateral frontoparietal polymicrogyria via multiple mechanisms. J. Biol. Chem. 286, 14215-14225 (2011).
68. M. Steinert, M. Wobus, C. Boltze, A. Schütz, M.Wahlbuhl, J. Hamann, G. Aust, Expression and regulation of CD97 in colorectal carcinoma cell lines and tumor tissues. Am. J. Pathol. 161, 1657-1667 (2002).
69. J. Galle, D. Sittig, I. Hanisch, M. Wobus, E. Wandel, M. Loeffler, G. Aust, Individual cell-based models of tumor-environment interactions: Multiple effects of CD97 on tumor invasion. Am. J. Pathol. 169, 1802-1811 (2006).
70. C. P. Ponting, K. Hofmann, P. Bork, A latrophilin/CL-1-like GPS domain in polycystin-1. Curr. Biol. 9, R585-R588 (1999).
71. G. W. Chang, M. Stacey, M. J. Kwakkenbos, J. Hamann, S. Gordon, H. H. Lin, Proteolytic cleavage of the EMR2 receptor requires both the extracellular stalk and the GPS motif. FEBS Lett. 547, 145-150 (2003).
72. T. C. Südhof, J. L. Goldstein, M. S. Brown, D. W. Russell, The LDL receptor gene: A mosaic of exons shared with different proteins. Science 228, 815-822 (1985).
73. R. Fredriksson, D. E. I. Gloriam, P. J. Höglund, M. C. Lagerström, H. B. Schiöth, There exist at least 30 human G-protein-coupled receptors with long Ser/Thr-rich N-termini. Biochem. Biophys. Res. Commun. 301, 725-734 (2003).
74. W. Wei, K. Hackmann, H. Xu, G. Germino, F. Qian, Characterization of cis-autoproteolysis of polycystin-1, the product of human polycystic kidney disease 1 gene. J. Biol. Chem. 282, 21729-21737 (2007).
75. T. Davies, R. Marians, R. Latif, The TSH receptor reveals itself. J. Clin. Invest. 110, 161-164 (2002).
76. C. C. Hsiao, K. F. Cheng, H. Y. Chen, Y. H. Chou, M. Stacey, G. W. Chang, H. H. Lin, Site-specific N-glycosylation regulates the GPS auto-proteolysis of CD97. FEBS Lett. 583, 3285-3290 (2009).
77. S. Prömel, M. Frickenhaus, S. Hughes, L. Mestek, D. Staunton, A.Woollard, I. Vakonakis, T. Schöneberg, R. Schnabel, A. P. Russ, T. Langenhan, The GPS motif is a molecular switch for bimodal activities of adhesion class G protein-coupled receptors. Cell Rep. 2, 321-331 (2012).
78. S. Prömel, H. Waller-Evans, J. Dixon, D. Zahn, W. H. Colledge, J. Doran, M. B. L. Carlton, J. Grosse, T. Schöneberg, A. P. Russ, T. Langenhan, Characterization and functional study of a cluster of four highly conserved orphan adhesion-GPCR in mouse. Dev. Dyn. 241, 1591-1602 (2012).
79. Z. Jin, I. Tietjen, L. Bu, L. Liu-Yesucevitz, S. K. Gaur, C. A. Walsh, X. Piao, Disease-associated mutations affect GPR56 protein trafficking and cell surface expression. Hum. Mol. Genet. 16, 1972-1985 (2007).
80. F. Qian, A. Boletta, A. K. Bhunia, H. Xu, L. Liu, A. K. Ahrabi, T. J. Watnick, F. Zhou, G. G. Germino, Cleavage of polycystin-1 requires the receptor for egg jelly domain and is disrupted by human autosomal-dominant polycystic kidney disease 1-associated mutations. Proc. Natl. Acad. Sci. U.S.A. 99, 16981-16986 (2002).
81. K. E. Volynski, J. P. Silva, V. G. Lelianova, M. Atiqur Rahman, C. Hopkins, Y. A. Ushkaryov, Latrophilin fragments behave as independent proteins that associate and signal on binding of LTXN4C. EMBO J. 23, 4423-4433 (2004).
82. Y. S. Huang, N. Y. Chiang, C. H. Hu, C. C. Hsiao, K. F. Cheng, W. P. Tsai, S. Yona, M. Stacey, S. Gordon, G. W. Chang, H. H. Lin, Activation of myeloid cell-specific adhesion class G protein-coupled receptor EMR2 via ligation-induced translocation and interaction of receptor subunits in lipid raft microdomains. Mol. Cell. Biol. 32, 1408-1420 (2012).
83. J. P. Silva, V. Lelianova, C. Hopkins, K. E. Volynski, Y. Ushkaryov, Functional cross-interaction of the fragments produced by the cleavage of distinct adhesion G-protein-coupled receptors. J. Biol. Chem. 284, 6495-6506 (2009).
84. J. P. Silva, Y. A. Ushkaryov, The latrophilins, "split- personality" receptors. Adv. Exp. Med. Biol. 706, 59-75 (2010).
85. B. Macao, D. G. A. Johansson, G. C. Hansson, T. Härd, Autoproteolysis coupled to protein folding in the SEA domain of the membrane-bound MUC1 mucin. Nat. Struct. Mol. Biol. 13, 71-76 (2006).
86. H. Matsui, B. R. Grubb, R. Tarran, S. H. Randell, J. T. Gatzy, C. W. Davis, R. C. Boucher, Evidence for periciliary liquid layer depletion, not abnormal ion composition, in the pathogenesis of cystic fibrosis airways disease. Cell 95, 1005-1015 (1998).
87. O. N. Karpus, H. Veninga, R. M. Hoek, D. Flierman, J. D. van Buul, C. C. Vandenakker, E. Vanbavel, M. E. Medof, R. A.W. van Lier, K. A. Reedquist, J. Hamann, Shear stress-dependent downregulation of the adhesion-G protein-coupled receptor CD97 on circulating leukocytes upon contact with its ligand CD55. J. Immunol. 190, 3740-3748 (2013).
88. Z. Kan, B. S. Jaiswal, J. Stinson, V. Janakiraman, D. Bhatt, H. M. Stern, P. Yue, P. M. Haverty, R. Bourgon, J. Zheng, M. Moorhead, S. Chaudhuri, L. P. Tomsho, B. A. Peters, K. Pujara, S. Cordes, D. P. Davis, V. E. H. Carlton,W. Yuan, L. Li,W.Wang, C. Eigenbrot, J. S. Kaminker, D. A. Eberhard, P. Waring, S. C. Schuster, Z. Modrusan, Z. Zhang, D. Stokoe, F. J. de Sauvage, M. Faham, S. Seshagiri, Diverse somatic mutation patterns and pathway alterations in human cancers. Nature 466, 869-873 (2010).
89. T. Qi, D. L. Hay, Structure-function relationships of the N-terminus of receptor activity-modifying proteins. Br. J. Pharmacol. 159, 1059-1068 (2010).
90. K. D. Little, M. E. Hemler, C. S. Stipp, Dynamic regulation of a GPCR-tetraspanin-G protein complex on intact cells: Central role of CD81 in facilitating GPR56-Gαq/11 association. Mol. Biol. Cell 15, 2375-2387 (2004).
91. J. Abe, T. Fukuzawa, S. Hirose, Cleavage of Ig-Hepta at a "SEA" module and at a conserved G protein-coupled receptor proteolytic site. J. Biol. Chem. 277, 23391-23398 (2002).
92. T. Moriguchi, K. Haraguchi, N. Ueda, M. Okada, T. Furuya, T. Akiyama, DREG, a developmentally regulated G protein-coupled receptor containing two conserved proteolytic cleavage sites. Genes Cells 9, 549-560 (2004).
93. M. Vallon, M. Essler, Proteolytically processed soluble tumor endothelial marker (TEM) 5 mediates endothelial cell survival during angiogenesis by linking integrin αvβ3 to glycosaminoglycans. J. Biol. Chem. 281, 34179-34188 (2006).
94. V. Krasnoperov, I. E. Deyev, O. V. Serova, C. Xu, Y. Lu, L. Buryanovsky, A. G. Gabibov, T. A. Neubert, A. G. Petrenko, Dissociation of the subunits of the calcium-independent receptor of a-latrotoxin as a result of two-step proteolysis. Biochemistry 48, 3230-3238 (2009).
95. D. Okajima, G. Kudo, H. Yokota, Brain-specific angiogenesis inhibitor 2 (BAI2) may be activated by proteolytic processing. J. Recept. Signal Transduct. Res. 30, 143-153 (2010).
96. C. J. Formstone, C. Moxon, J. Murdoch, P. Little, I. Mason, Basal enrichment within neuroepithelia suggests novel function(s) for Celsr1 protein. Mol. Cell. Neurosci. 44, 210-222 (2010).
97. S.M. Cork, B. Kaur, N. S. Devi, L. Cooper, J. H. Saltz, E. M. Sandberg, S. Kaluz, E. G. Van Meir, A proprotein convertase/MMP-14 proteolytic cascade releases a novel 40kDa vasculostatin from tumor suppressor BAI1. Oncogene 31, 5144-5152 (2012).
98. T. Fukuzawa, S. Hirose, Multiple processing of Ig-Hepta/GPR116, a G protein-coupled receptor with immunoglobulin (Ig)-like repeats, and generation of EGF2-like fragment. J. Biochem. 140, 445-452 (2006).
99. S. J. Bray, Notch signalling: A simple pathway becomes complex. Nat. Rev. Mol. Cell Biol. 7, 678-689 (2006).
100. M. Vallon, P. Aubele, K. P. Janssen, M. Essler, Thrombin-induced shedding of tumour endothelial marker 5 and exposure of its RGD motif are regulated by cell-surface protein disulfide-isomerase. Biochem. J. 441, 937-944 (2012).
101. T. Wang, Y. Ward, L. Tian, R. Lake, L. Guedez, W. G. Stetler-Stevenson, K. Kelly, CD97, an adhesion receptor on inflammatory cells, stimulates angiogenesis through binding integrin counterreceptors on endothelial cells. Blood 105, 2836-2844 (2005).
102. J. T. Koh, H. Kook, H. J. Kee, Y. W. Seo, B. C. Jeong, J. H. Lee, M. Y. Kim, K. C. Yoon, S. Jung, K. K. Kim, Extracellular fragment of brain-specific angiogenesis inhibitor 1 suppresses endothelial cell proliferation by blocking αvβ5 integrin. Exp. Cell Res. 294, 172-184 (2004).
103. B. Kaur, S. M. Cork, E. M. Sandberg, N. S. Devi, Z. Zhang, P. A. Klenotic, M. Febbraio, H. Shim, H. Mao, C. Tucker-Burden, R. L. Silverstein, D. J. Brat, J. J. Olson, E. G. VanMeir, Vasculostatin inhibits intracranial glioma growth and negatively regulates in vivo angiogenesis through a CD36-dependent mechanism. Cancer Res. 69, 1212-1220 (2009).
104. J. Hamann, J. O. Wishaupt, R. A. van Lier, T. J. Smeets, F. C. Breedveld, P. P. Tak, Expression of the activation antigen CD97 and its ligand CD55 in rheumatoid synovial tissue. Arthritis Rheum. 42, 650-658 (1999).
105. D. M. de Groot, G. Vogel, J. Dulos, L. Teeuwen, K. Stebbins, J. Hamann, B. M. Owens, H. van Eenennaam, E. Bos, A. M. Boots, Therapeutic antibody targeting of CD97 in experimental arthritis: The role of antigen expression, shedding, and internalization on the pharmacokinetics of anti-CD97 monoclonal antibody 1B2. J. Immunol. 183, 4127-4134 (2009).
106. P. P. Humphrey, E. A. Barnard, International Union of Pharmacology. XIX. The IUPHAR receptor code: A proposal for an alphanumeric classification system. Pharmacol. Rev. 50, 271-277 (1998).
107. J. Hamann, H. Veninga, D. M. de Groot, L. Visser, C. L. Hofstra, P. P. Tak, J. D. Laman, A. M. Boots, H. van Eenennaam, CD97 in leukocyte trafficking. Adv. Exp. Med. Biol. 706, 128-137 (2010).
108. J. P. Pin, T. Galvez, L. Prézeau, Evolution, structure, and activation mechanism of family 3/C G-protein-coupled receptors. Pharmacol. Ther. 98, 325-354 (2003).
109. S. G. Rasmussen, H. J. Choi, D. M. Rosenbaum, T. S. Kobilka, F. S. Thian, P. C. Edwards, M. Burghammer, V. R. Ratnala, R. Sanishvili, R. F. Fischetti, G. F. Schertler, W. I. Weis, B. K. Kobilka, Crystal structure of the human b2 adrenergic G-protein-coupled receptor. Nature 450, 383-387 (2007).
110. M. P. Bokoch, Y. Zou, S. G. F. Rasmussen, C. W. Liu, R. Nygaard, D. M. Rosenbaum, J. J. Fung, H. J. Choi, F. S. Thian, T. S. Kobilka, J. D. Puglisi, W. I. Weis, L. Pardo, R. S. Prosser, L. Mueller, B. K. Kobilka, Ligand-specific regulation of the extracellular surface of a G-protein-coupled receptor. Nature 463, 108-112 (2010).
111. S. G. F. Rasmussen, B. T. DeVree, Y. Zou, A. C. Kruse, K. Y. Chung, T. S. Kobilka, F. S. Thian, P. S. Chae, E. Pardon, D. Calinski, J. M. Mathiesen, S. T. A. Shah, J. A. Lyons, M. Caffrey, S. H. Gellman, J. Steyaert, G. Skiniotis, W. I. Weis, R. K. Sunahara, B. K. Kobilka, Crystal structure of the b2 adrenergic receptor-Gs protein complex. Nature 477, 549-555 (2011).
112. J. Gupte, G. Swaminath, J. Danao, H. Tian, Y. Li, X. Wu, Signaling property study of adhesion G-protein-coupled receptors. FEBS Lett. 586, 1214-1219 (2012).
113. J. Bohnekamp, T. Schöneberg, Cell adhesion receptor GPR133 couples to Gs protein. J. Biol. Chem. 286, 41912-41916 (2011).
114. M. Schwartz, Rho signalling at a glance. J. Cell Sci. 117, 5457-5458 (2004).
115. D. P. Siderovski, F. S. Willard, The GAPs, GEFs, and GDIs of heterotrimeric G-protein alpha subunits. Int. J. Biol. Sci. 1, 51-66 (2005).
116. T. L. Gumienny, E. Brugnera, A. C. Tosello-Trampont, J. M. Kinchen, L. B. Haney, K. Nishiwaki, S. F. Walk, M. E. Nemergut, I. G. Macara, R. Francis, T. Schedl, Y. Qin, L. Van Aelst, M. O. Hengartner, K. S. Ravichandran, CED-12/ELMO, a novel member of the CrkII/Dock180/Rac pathway, is required for phagocytosis and cell migration. Cell 107, 27-41 (2001).
117. L. L. Wong, P. N. Adler, Tissue polarity genes of Drosophila regulate the subcellular location for prehair initiation in pupal wing cells. J. Cell Biol. 123, 209-221 (1993).
118. D. Strutt, The planar polarity pathway. Curr. Biol. 18, R898-R902 (2008).
119. J. Wu, M. Mlodzik, A quest for the mechanism regulating global planar cell polarity of tissues. Trends Cell Biol. 19, 295-305 (2009).
120. M. Simons, M. Mlodzik, Planar cell polarity signaling: From fly development to human disease. Annu. Rev. Genet. 42, 517-540 (2008).
121. D. I. Strutt, U. Weber, M. Mlodzik, The role of RhoA in tissue polarity and Frizzled signalling. Nature 387, 292-295 (1997).
122. P. A. Lawrence, J. Casal, G. Struhl, Cell interactions and planar polarity in the abdominal epidermis of Drosophila. Development 131, 4651-4664 (2004).
123. F. Carreira-Barbosa, M. Kajita, M. Kajita, V. Morel, H.Wada, H. Okamoto, A. Martinez Arias, Y. Fujita, S. W. Wilson, M. Tada, Flamingo regulates epiboly and convergence/extension movements through cell cohesive and signalling functions during zebrafish gastrulation. Development 136, 383-392 (2009).
124. S. Becker, E. Wandel, M. Wobus, R. Schneider, S. Amasheh, D. Sittig, C. Kerner, R. Naumann, J. Hamann, G. Aust, Overexpression of CD97 in intestinal epithelial cells of transgenic mice attenuates colitis by strengthening adherens junctions. PLoS One 5, e8507 (2010).
125. G. Aust, W. Eichler, S. Laue, I. Lehmann, N. E. Heldin, O. Lotz, W. A. Scherbaum, H. Dralle, C. Hoang-Vu, CD97: A dedifferentiation marker in human thyroid carcinomas. Cancer Res. 57, 1798-1806 (1997).
126. Y. Ward, R. Lake, J. J. Yin, C. D. Heger, M. Raffeld, P. K. Goldsmith, M. Merino, K. Kelly, LPA receptor heterodimerizes with CD97 to amplify LPA-initiated RHO-dependent signaling and invasion in prostate cancer cells. Cancer Res. 71, 7301-7311 (2011).
127. Y. Ward, R. Lake, P. L. Martin, K. Killian, P. Salerno, T. Wang, P. Meltzer, M. Merino, S. Y. Cheng, M. Santoro, G. Garcia-Rostan, K. Kelly, CD97 amplifies LPA receptor signaling and promotes thyroid cancer progression in a mouse model. Oncogene 10.1038/onc.2012.301 (2012).
128. T. Iguchi, K. Sakata, K. Yoshizaki, K. Tago, N. Mizuno, H. Itoh, Orphan G protein-coupled receptor GPR56 regulates neural progenitor cell migration via a G a 12/13 and Rho pathway. J. Biol. Chem. 283, 14469-14478 (2008).
129. H. Kimura, T. Usui, A. Tsubouchi, T. Uemura, Potential dual molecular interaction of the Drosophila 7-pass transmembrane cadherin Flamingo in dendritic morphogenesis. J. Cell Sci. 119, 1118-1129 (2006).
130. J. V. Olsen, B. Blagoev, F. Gnad, B. Macek, C. Kumar, P. Mortensen, M. Mann, Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 127, 635-648 (2006).
131. R. P. Munton, R. Tweedie-Cullen, M. Livingstone-Zatchej, F. Weinandy, M. Waidelich, D. Longo, P. Gehrig, F. Potthast, D. Rutishauser, B. Gerrits, C. Panse, R. Schlapbach, I. M. Mansuy, Qualitative and quantitative analyses of protein phosphorylation in naive and stimulated mouse synaptosomal preparations. Mol. Cell. Proteomics 6, 283-293 (2007).
132. K. Rikova, A. Guo, Q. Zeng, A. Possemato, J. Yu, H. Haack, J. Nardone, K. Lee, C. Reeves, Y. Li, Y. Hu, Z. Tan, M. Stokes, L. Sullivan, J. Mitchell, R. Wetzel, J. Macneill, J. M. Ren, J. Yuan, C. E. Bakalarski, J. Villen, J. M. Kornhauser, B. Smith, D. Li, X. Zhou, S. P. Gygi, T. L. Gu, R. D. Polakiewicz, J. Rush, M. J. Comb, Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell 131, 1190-1203 (2007).
133. N. Dephoure, C. Zhou, J. Villén, S. A. Beausoleil, C. E. Bakalarski, S. J. Elledge, S. P. Gygi, A quantitative atlas of mitotic phosphorylation. Proc. Natl. Acad. Sci. U.S.A. 105, 10762-10767 (2008).
134. J. V. Olsen, M. Vermeulen, A. Santamaria, C. Kumar, M. L. Miller, L. J. Jensen, F. Gnad, J. Cox, T. S. Jensen, E. A. Nigg, S. Brunak, M. Mann, Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci. Signal. 3, ra3 (2010).
135. C. Jørgensen, A. Sherman, G. I. Chen, A. Pasculescu, A. Poliakov, M. Hsiung, B. Larsen, D. G. Wilkinson, R. Linding, T. Pawson, Cell-specific information processing in segregating populations of Eph receptor ephrin-expressing cells. Science 326, 1502-1509 (2009).
136. K. Imami, N. Sugiyama, Y. Kyono, M. Tomita, Y. Ishihama, Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column. Anal. Sci. 24, 161-166 (2008).
137. D. Van Hoof, J. Muñoz, S. R. Braam, M. W. H. Pinkse, R. Linding, A. J. R. Heck, C. L. Mummery, J. Krijgsveld, Phosphorylation dynamics during early differentiation of human embryonic stem cells. Cell Stem Cell 5, 214-226 (2009).
138. L. Yang, G. Chen, S. Mohanty, G. Scott, F. Fazal, A. Rahman, S. Begum, R. O. Hynes, L. Xu, GPR56 regulates VEGF production and angiogenesis during melanoma progression. Cancer Res. 71, 5558-5568 (2011).
139. G. Vassart, L. Pardo, S. Costagliola, A molecular dissection of the glycoprotein hormone receptors. Trends Biochem. Sci. 29, 119-126 (2004).
140. J. E. Kim, J. M. Han, C. R. Park, K. J. Shin, C. Ahn, J. Y. Seong, J. I. Hwang, Splicing variants of the orphan G-protein-coupled receptor GPR56 regulate the activity of transcription factors associated with tumorigenesis. J. Cancer Res. Clin. Oncol. 136, 47-53 (2010).
141. K. Fuxe, D. O. Borroto-Escuela, D. Marcellino, W. Romero-Fernandez, M. Frankowska, D. Guidolin, M. Filip, L. Ferraro, A. S. Woods, A. Tarakanov, F. Ciruela, L. F. Agnati, S. Tanganelli, GPCR heteromers and their allosteric receptor-receptor interactions. Curr. Med. Chem. 19, 356-363 (2012).
142. P. Maurice, M. Kamal, R. Jockers, Asymmetry of GPCR oligomers supports their functional relevance. Trends Pharmacol. Sci. 32, 514-520 (2011).
143. J. Abe, H. Suzuki, M. Notoya, T. Yamamoto, S. Hirose, Ig-Hepta, a novel member of the G protein-coupled hepta-helical receptor (GPCR) family that has
144. T. Nechiporuk, L. D. Urness, M. T. Keating, ETL, a novel seven-transmembrane receptor that is developmentally regulated in the heart. ETL is a member of the secretin family and belongs to the epidermal growth factor-seven-transmembrane subfamily. J. Biol. Chem. 276, 4150-4157 (2001).
145. J. Q. Davies, G. W. Chang, S. Yona, S. Gordon, M. Stacey, H. H. Lin, The role of receptor oligomerization in modulating the expression and function of leukocyte adhesion-G protein-coupled receptors. J. Biol. Chem. 282, 27343-27353 (2007).
146. P. L. Chen, T. R. Clandinin, The cadherin Flamingo mediates level-dependent interactions that guide photoreceptor target choice in Drosophila. Neuron 58, 26-33 (2008).
147. T. Maerker, E. van Wijk, N. Overlack, F. F. J. Kersten, J. McGee, T. Goldmann, E. Sehn, R. Roepman, E. J. Walsh, H. Kremer, U. Wolfrum, A novel Usher protein network at the periciliary reloading point between molecular transport machineries in vertebrate photoreceptor cells. Hum. Mol. Genet. 17, 71-86 (2008).
148. E. vanWijk, B. van der Zwaag, T. Peters, U. Zimmermann, H. Te Brinke, F. F. J. Kersten, T. Märker, E. Aller, L. H. Hoefsloot, C. W. R. J. Cremers, F. P. M. Cremers, U. Wolfrum, M. Knipper, R. Roepman, H. Kremer, The DFNB31 gene product whirlin connects to the Usher protein network in the cochlea and retina by direct association with USH2A and VLGR1. Hum. Mol. Genet. 15, 751-765 (2006).
149. M. Zallocchi, D. T. Meehan, D. Delimont, J. Rutledge, M. A. Gratton, J. Flannery, D. Cosgrove, Role for a novel Usher protein complex in hair cell synaptic maturation. PLoS One 7, e30573 (2012).
150. T. Shiratsuchi, M. Futamura, K. Oda, H. Nishimori, Y. Nakamura, T. Tokino, Cloning and characterization of BAI-associated protein 1: A PDZ domain-containing protein that interacts with BAI1. Biochem. Biophys. Res. Commun. 247, 597-604 (1998).
151. S. Zencir, M. Ovee, M. J. Dobson, M. Banerjee, Z. Topcu, S. Mohanty, Identification of brain-specific angiogenesis inhibitor 2 as an interaction partner of glutaminase interacting protein. Biochem. Biophys. Res. Commun. 411, 792-797 (2011).
152. H. Zitzer, H. H. Hönck, D. Bächner, D. Richter, H. J. Kreienkamp, Somatostatin receptor interacting protein defines a novel family of multidomain proteins present in human and rodent brain. J. Biol. Chem. 274, 32997-33001 (1999).
153. T. M. Boeckers, C. Winter, K. H. Smalla, M. R. Kreutz, J. Bockmann, C. Seidenbecher, C. C. Garner, E. D. Gundelfinger, Proline-rich synapse-associated proteins ProSAP1 and ProSAP2 interact with synaptic proteins of the SAPAP/GKAP family. Biochem. Biophys. Res. Commun. 264, 247-252 (1999).
154. H. J. Kreienkamp, H. Zitzer, E. D. Gundelfinger, D. Richter, T. M. Bockers, The calcium-independent receptor for α-latrotoxin from human and rodent brains interacts with members of the ProSAP/SSTRIP/Shank family of multidomain proteins. J. Biol. Chem. 275, 32387-32390 (2000).
155. Y. Yamamoto, K. Irie, M. Asada, A. Mino, K. Mandai, Y. Takai, Direct binding of the human homologue of the Drosophila disc large tumor suppressor gene to seven-pass transmembrane proteins, tumor endothelial marker 5 (TEM5), and a novel TEM5-like protein. Oncogene 23, 3889-3897 (2004).
156. G. Milligan, J. H. White, Protein-protein interactions at G-protein-coupled receptors. Trends Pharmacol. Sci. 22, 513-518 (2001).
157. S. Tobaben, T. C. Südhof, B. Stahl, Genetic analysis of α-latrotoxin receptors reveals functional interdependence of CIRL/latrophilin 1 and neurexin 1α. J. Biol. Chem. 277, 6359-6365 (2002).
158. M. Arcos-Burgos, M. Jain, M. T. Acosta, S. Shively, H. Stanescu, D. Wallis, S. Domené, J. I. Vélez, J. D. Karkera, J. Balog, K. Berg, R. Kleta, W. A. Gahl, E. Roessler, R. Long, J. Lie, D. Pineda, A. C. Londoño, J. D. Palacio, A. Arbelaez, F. Lopera, J. Elia, H. Hakonarson, S. Johansson, P. M. Knappskog, J. Haavik, M. Ribases, B. Cormand, M. Bayes, M. Casas, J. A. Ramos-Quiroga, A. Hervas, B. S. Maher, S. V. Faraone, C. Seitz, C. M. Freitag, H. Palmason, J. Meyer, M. Romanos, S. Walitza, U. Hemminger, A. Warnke, J. Romanos, T. Renner, C. Jacob, K. P. Lesch, J. Swanson, A. Vortmeyer, J. E. Bailey-Wilson, F. X. Castellanos, M. Muenke, A common variant of the latrophilin 3 gene, LPHN3, confers susceptibility to ADHD and predicts effectiveness of stimulant medication. Mol. Psychiatry 15, 1053-1066 (2010).
159. M. Lange, W. Norton, M. Coolen, M. Chaminade, S. Merker, F. Proft, A. Schmitt, P. Vernier, K. P. Lesch, L. Bally-Cuif, The ADHD-susceptibility gene lphn3.1 modulates dopaminergic neuron formation and locomotor activity during zebrafish development. Mol. Psychiatry 17, 946-954 (2012).
160. J. Xiao, H. Jiang, R. Zhang, G. Fan, Y. Zhang, D. Jiang, H. Li, Augmented cardiac hypertrophy in response to pressure overload in mice lacking ELTD1. PLoS One 7, e35779 (2012).
161. H. H. Lin, D. E. Faunce, M. Stacey, A. Terajewicz, T. Nakamura, J. Zhang-Hoover, M. Kerley, M. L. Mucenski, S. Gordon, J. Stein-Streilein, The macrophage F4/80 receptor is required for the induction of antigen-specific efferent regulatory T cells in peripheral tolerance. J. Exp. Med. 201, 1615-1625 (2005).
162. F. Kuhnert, M. R. Mancuso, A. Shamloo, H. T. Wang, V. Choksi, M. Florek, H. Su, M. Fruttiger, W. L. Young, S. C. Heilshorn, C. J. Kuo, Essential regulation of CNS angiogenesis by the orphan G protein-coupled receptor GPR124. Science 330, 985-989 (2010).
163. K. D. Anderson, L. Pan, X. M. Yang, V. C. Hughes, J. R. Walls, M. G. Dominguez, M. V. Simmons, P. Burfeind, Y. Xue, Y. Wei, L. E. Macdonald, G. Thurston, C. Daly, H. C. Lin, A. N. Economides, D. M. Valenzuela, A. J. Murphy, G. D. Yancopoulos, N. W. Gale, Angiogenic sprouting into neural tissue requires Gpr124, an orphan G protein-coupled receptor. Proc. Natl. Acad. Sci. U.S.A. 108, 2807-2812 (2011).
164. M. Cullen, M. K. Elzarrad, S. Seaman, E. Zudaire, J. Stevens, M. Y. Yang, X. Li, A. Chaudhary, L. Xu, M. B. Hilton, D. Logsdon, E. Hsiao, E. V. Stein, F. Cuttitta, D. C. Haines, K. Nagashima, L. Tessarollo, B. St Croix, GPR124, an orphan G protein-coupled receptor, is required for CNS-specific vascularization and establishment of the blood-brain barrier. Proc. Natl. Acad. Sci. U.S.A. 108, 5759-5764 (2011).
165. J. Chae, M. J. Kim, J. H. Goo, S. Collier, D. Gubb, J. Charlton, P. N. Adler, W. J. Park, The Drosophila tissue polarity gene starry night encodes a member of the protocadherin family. Development 126, 5421-5429 (1999).
166. J. A. Curtin, E. Quint, V. Tsipouri, R. M. Arkell, B. Cattanach, A. J. Copp, D. J. Henderson, N. Spurr, P. Stanier, E. M. Fisher, P. M. Nolan, K. P. Steel, S. D. M. Brown, I. C. Gray, J. N. Murdoch, Mutation of Celsr1 disrupts planar polarity of inner ear hair cells and causes severe neural tube defects in the mouse. Curr. Biol. 13, 1129-1133 (2003).
167. A. Ravni, Y. Qu, A. M. Goffinet, F. Tissir, Planar cell polarity cadherin Celsr1 regulates skin hair patterning in the mouse. J. Invest. Dermatol. 129, 2507-2509 (2009).
168. Y. Qu, D. M. Glasco, L. Zhou, A. Sawant, A. Ravni, B. Fritzsch, C. Damrau, J. N. Murdoch, S. Evans, S. L. Pfaff, C. Formstone, A. M. Goffinet, A. Chandrasekhar, F. Tissir, Atypical cadherins Celsr1-3 differentially regulate migration of facial branchiomotor neurons in mice. J. Neurosci. 30, 9392-9401 (2010).
169. S. Kathiresan, O. Melander, C. Guiducci, A. Surti, N. P. Burtt, M. J. Rieder, G. M. Cooper, C. Roos, B. F. Voight, A. S. Havulinna, B. Wahlstrand, T. Hedner, D. Corella, E. S. Tai, J. M. Ordovas, G. Berglund, E. Vartiainen, P. Jousilahti, B. Hedblad, M. R. Taskinen, C. Newton-Cheh, V. Salomaa, L. Peltonen, L. Groop, D. M. Altshuler, M. Orho-Melander, Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans. Nat. Genet. 40, 189-197 (2008).
170. Myocardial Infarction Genetics Consortium,S. Kathiresan, B. F. Voight, S. Purcell, K. Musunuru, D. Ardissino, P. M. Mannucci, S. Anand, J. C. Engert, N. J. Samani, H. Schunkert, J. Erdmann, M. P. Reilly, D. J. Rader, T. Morgan, J. A. Spertus, M. Stoll, D. Girelli, P. P. McKeown, C. C. Patterson, D. S. Siscovick, C. J. O'Donnell, R. Elosua, L. Peltonen, V. Salomaa, S. M. Schwartz, O. Melander, D. Altshuler, D. Ardissino, P. A. Merlini, C. Berzuini, L. Bernardinelli, F. Peyvandi, M. Tubaro, P. Celli, M. Ferrario, R. Fetiveau, N. Marziliano, G. Casari, M. Galli, F. Ribichini, M. Rossi, F. Bernardi, P. Zonzin, A. Piazza, P. M.Mannucci, S.M. Schwartz, D. S. Siscovick, J. Yee, Y. Friedlander, R. Elosua, J. Marrugat, G. Lucas, I. Subirana, J. Sala, R. Ramos, S. Kathiresan, J. B. Meigs, G. Williams, D. M. Nathan, C. A. MacRae, C. J. O'Donnell, V. Salomaa, A. S. Havulinna, L. Peltonen, O. Melander, G. Berglund, B. F. Voight, S. Kathiresan, J. N. Hirschhorn, R. Asselta, S. Duga, M. Spreafico, K. Musunuru, M. J. Daly, S. Purcell, B. F. Voight, S. Purcell, J. Nemesh, J. M. Korn, S. A. McCarroll, S. M. Schwartz, J. Yee, S. Kathiresan, G. Lucas, I. Subirana, R. Elosua, A. Surti, C. Guiducci, L. Gianniny, D. Mirel, M. Parkin, N. Burtt, S. B. Gabriel, N. J. Samani, J. R. Thompson, P. S. Braund, B. J. Wright, A. J. Balmforth, S. G. Ball, A. S. Hall; Wellcome Trust Case Control Consortium, H. Schunkert, J. Erdmann, P. Linsel-Nitschke, W. Lieb, A. Ziegler, I. König, C. Hengstenberg, M. Fischer, K. Stark, A. Grosshennig, M. Preuss, H.-E. Wichmann, S. Schreiber, H. Schunkert, N. J. Samani, J. Erdmann, W. Ouwehand, C. Hengstenberg, P. Deloukas, M. Scholz, F. Cambien, M. P. Reilly, M. Li, Z. Chen, R. Wilensky, W. Matthai, A. Qasim, H. H. Hakonarson, J. Devaney, M.-S. Burnett, A. D. Pichard, K. M. Kent, L. Satler, J. M. Lindsay, R. Waksman, C. W. Knouff, D. M. Waterworth, M. C. Walker, V. Mooser, S. E. Epstein, D. J. Rader, T. Scheffold, K. Berger, M. Stoll, A. Huge, D. Girelli, N. Martinelli,O. Olivieri, R. Corrocher, T. Morgan, J. A. Spertus, P. McKeown,C.C. Patterson, H. Schunkert, E. Erdmann, P. Linsel-Nitschke, W. Lieb, A. Ziegler, I. R. König, C. Hengstenberg, M. Fischer, K. Stark, A. Grosshennig, M. Preuss, H.-E.Wichmann, S. Schreiber, H. Hólm, G. Thorleifsson, U. Thorsteinsdottir, K. Stefansson, J. C. Engert, R. Do, C. Xie, S. Anand, S. Kathiresan, D. Ardissino, P. M. Mannucci, D. Siscovick, C. J. O'Donnell, N. J. Samani, O. Melander, R. Elosua, L. Peltonen, V. Salomaa, S. M. Schwartz, D. Altshuler, Genomewide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants. Nat. Genet. 41, 334-341 (2009).
171. F. Tissir, Y. Qu, M. Montcouquiol, L. Zhou, K. Komatsu, D. Shi, T. Fujimori, J. Labeau, D. Tyteca, P. Courtoy, Y. Poumay, T. Uemura, A. M. Goffinet, Lack of cadherins Celsr2 and Celsr3 impairs ependymal ciliogenesis, leading to fatal hydrocephalus. Nat. Neurosci. 13, 700-707 (2010).
172. L. Zhou, Y. Qu, F. Tissir, A. M. Goffinet, Role of the atypical cadherin Celsr3 during development of the internal capsule. Cereb. Cortex 19 (suppl. 1), i114-i119 (2009).
173. C. Cortijo, M. Gouzi, F. Tissir, A. Grapin-Botton, Planar cell polarity controls pancreatic beta cell differentiation and glucose homeostasis. Cell Rep. 2, 1593-1606 (2012).
174. A. Tönjes, M. Koriath, D. Schleinitz, K. Dietrich, Y. Böttcher, N. W. Rayner, P. Almgren, B. Enigk, O. Richter, S. Rohm, A. Fischer-Rosinsky, A. Pfeiffer, K. Hoffmann, K. Krohn, G. Aust, J. Spranger, L. Groop, M. Blüher, P. Kovacs, M. Stumvoll, Genetic variation in GPR133 is associated with height: Genome wide association study in the self-contained population of Sorbs. Hum. Mol. Genet. 18, 4662-4668 (2009).
175. Y. F. Chan, F. C. Jones, E. McConnell, J. Bryk, L. Bünger, D. Tautz, Parallel selection mapping using artificially selected mice reveals body weight control loci. Curr. Biol. 22, 794-800 (2012).
176. T. Nie, X. Hui, X. Gao, K. Li,W. Lin, X. Xiang, M. Ding, Y. Kuang, A. Xu, J. Fei, Z.Wang, D. Wu, Adipose tissue deletion of Gpr116 impairs insulin sensitivity through modulation of adipose function. FEBS Lett. 586, 3618-3625 (2012).
177. D. Okajima, G. Kudo, H. Yokota, Antidepressant-like behavior in brain-specific angiogenesis inhibitor 2-deficient mice. J. Physiol. Sci. 61, 47-54 (2011).
178. G. Antoni, P. E. Morange, Y. Luo, N. Saut, G. Burgos, S. Heath, M. Germain, C. Biron-Andreani, J. F. Schved, G. Pernod, P. Galan, D. Zelenika, M. C. Alessi, L. Drouet, S. Visvikis-Siest, P. S. Wells, M. Lathrop, J. Emmerich, D. A. Tregouet, F. Gagnon, A multi-stage multi-design strategy provides strong evidence that the BAI3 locus is associated with early-onset venous thromboembolism. J. Thromb. Haemost. 8, 2671-2679 (2010).
179. S. Li, Z. Jin, S. Koirala, L. Bu, L. Xu, R. O. Hynes, C. A.Walsh, G. Corfas, X. Piao, GPR56 regulates pial basement membrane integrity and cortical lamination. J. Neurosci. 28, 5817-5826 (2008).
180. G. Chen, L. Yang, S. Begum, L. Xu, GPR56 is essential for testis development and male fertility in mice. Dev. Dyn. 239, 3358-3367 (2010).
181. B. Davies, C. Baumann, C. Kirchhoff, R. Ivell, R. Nubbemeyer, U. F. Habenicht, F. Theuring, U. Gottwald, Targeted deletion of the epididymal receptor HE6 results in fluid dysregulation and male infertility. Mol. Cell. Biol. 24, 8642-8648 (2004).
182. N. Soranzo, F. Rivadeneira, U. Chinappen-Horsley, I. Malkina, J. B. Richards, N. Hammond, L. Stolk, A. Nica, M. Inouye, A. Hofman, J. Stephens, E. Wheeler, P. Arp, R. Gwilliam, P. M. Jhamai, S. Potter, A. Chaney, M. J. R. Ghori, R. Ravindrarajah, S. Ermakov, K. Estrada, H. A. P. Pols, F. M. Williams, W. L. McArdle, J. B. van Meurs, R. J. F. Loos, E. T.Dermitzakis, K. R. Ahmadi, D. J. Hart,W.H. Ouwehand, N. J. Wareham, I. Barroso, M. S. Sandhu, D. P. Strachan, G. Livshits, T. D. Spector, A. G. Uitterlinden, P. Deloukas, Meta-analysis of genome-wide scans for human adult stature identifies novel loci and associations with measures of skeletal frame size. PLoS Genet. 5, e1000445 (2009).
183. D. B. Hancock, M. Eijgelsheim, J. B. Wilk, S. A. Gharib, L. R. Loehr, K. D. Marciante, N. Franceschini, Y. M. T. A. van Durme, T. H. Chen, R. G. Barr, M. B. Schabath, D. J. Couper, G. G. Brusselle, B. M. Psaty, C. M. van Duijn, J. I. Rotter, A. G. Uitterlinden, A. Hofman, N. M. Punjabi, F. Rivadeneira, A. C. Morrison, P. L. Enright, K. E. North, S. R. Heckbert, T. Lumley, B. H. C. Stricker, G. T. O'Connor, S. J. London, Meta-analyses of genome-wide association studies identify multiple loci associated with pulmonary function. Nat. Genet. 42, 45-52 (2010).
184. K. R.Monk, S.G. Naylor, T. D.Glenn, S.Mercurio, J. R. Perlin, C. Dominguez, C. B.Moens, W. S. Talbot, A G protein-coupled receptor is essential for Schwann cells to initiate myelination. Science 325, 1402-1405 (2009).
185. H. Waller-Evans, S. Prömel, T. Langenhan, J. Dixon, D. Zahn, W. H. Colledge, J. Doran, M. B. L. Carlton, B. Davies, S. A. J. R. Aparicio, J. Grosse, A. P. Russ, The orphan adhesion-GPCR GPR126 is required for embryonic development in the mouse. PLoS One 5, e14047 (2010).
186. K. R. Monk, K. Oshima, S. Jörs, S. Heller, W. S. Talbot, Gpr126 is essential for peripheral nerve development and myelination in mammals. Development 138, 2673-2680 (2011).
187. J. Nakayama, Y. H. Fu, A. M. Clark, S. Nakahara, K. Hamano, N. Iwasaki, A. Matsui, T. Arinami, L. J. Ptácek, A nonsense mutation of the MASS1 gene in a family with febrile and afebrile seizures. Ann. Neurol. 52, 654-657 (2002).
188. M. D. Weston, M. W. J. Luijendijk, K. D. Humphrey, C. Möller, W. J. Kimberling, Mutations in the VLGR1 gene implicate G-protein signaling in the pathogenesis of Usher syndrome type II. Am. J. Hum. Genet. 74, 357-366 (2004).
189. S. B. Schwartz, T. S. Aleman, A. V. Cideciyan, E. A.M.Windsor, A. Sumaroka, A. J. Roman, T. Rane, E. E. Smilko, J. Bennett, E. M. Stone, W. J. Kimberling, X. Z. Liu, S. G. Jacobson, Disease expression in Usher syndrome caused by VLGR1 gene mutation (USH2C) and comparison with USH2A phenotype. Invest. Ophthalmol. Vis. Sci. 46, 734-743 (2005).
190. T. Urano, M. Shiraki, H. Yagi, M. Ito, N. Sasaki, M. Sato, Y. Ouchi, S. Inoue, GPR98/Gpr98 gene is involved in the regulation of human and mouse bone mineral density. J. Clin. Endocrinol. Metab. 97, E565-E574 (2012).
191. S. L. Skradski, A. M. Clark, H. Jiang, H. S. White, Y. H. Fu, L. J. Ptácek, A novel gene causing a mendelian audiogenic mouse epilepsy. Neuron 31, 537-544 (2001).
192. D. R. McMillan, P. C. White, Loss of the transmembrane and cytoplasmic domains of the very large G-protein-coupled receptor-1 (VLGR1 or Mass1) causes audiogenic seizures in mice. Mol. Cell. Neurosci. 26, 322-329 (2004).
193. H. Yagi, Y. Takamura, T. Yoneda, D. Konno, Y. Akagi, K. Yoshida, M. Sato, Vlgr1 knockout mice show audiogenic seizure susceptibility. J. Neurochem. 92, 191-202 (2005).
194. H. Yagi, H. Tokano, M. Maeda, T. Takabayashi, T. Nagano, H. Kiyama, S. Fujieda, K. Kitamura, M. Sato, Vlgr1 is required for proper stereocilia maturation of cochlear hair cells. Genes Cells 12, 235-250 (2007).
195. M. L. O'Sullivan, J. deWit, J. N. Savas, D. Comoletti, S. Otto-Hitt, J. R. Yates, A. Ghosh, FLRT proteins are endogenous latrophilin ligands and regulate excitatory synapse development. Neuron 73, 903-910 (2012).
196. S. Mühlfeld, H. P. Schmitt-Wrede, A. Harder, F. Wunderlich, FMRFamide-like neuropeptides as putative ligands of the latrophilin-like HC110-R from Haemonchus contortus. Mol. Biochem. Parasitol. 164, 162-164 (2009).
197. Y. M. Qian, M. Haino, K. Kelly, W. C. Song, Structural characterization of mouse CD97 and study of its specific interaction with the murine decay-accelerating factor (DAF, CD55). Immunology 98, 303-311 (1999).
198. M. A. Rahman, A. C. Ashton, F. A. Meunier, B. A. Davletov, J. O. Dolly, Y. A. Ushkaryov, Norepinephrine exocytosis stimulated by a-latrotoxin requires both external and stored Ca2+ and is mediated by latrophilin, G proteins and phospholipase C. Philos. Trans. R. Soc. Lond. B Biol. Sci. 354, 379-386 (1999).
199. O. V. Serova, N. V. Popova, I. E. Deev, A. G. Petrenko, Identification of proteins in complexes with a-latrotoxin receptors. Bioorg. Khim. 34, 747-753 (2008).
200. Y. Shima, S. Y. Kawaguchi, K. Kosaka, M. Nakayama, M. Hoshino, Y. Nabeshima, T. Hirano, T. Uemura, Opposing roles in neurite growth control by two seven-pass transmembrane cadherins. Nat. Neurosci. 10, 963-969 (2007).
201. S. Shashidhar, G. Lorente, U. Nagavarapu, A. Nelson, J. Kuo, J. Cummins, K. Nikolich, R. Urfer, E. D. Foehr, GPR56 is a GPCR that is overexpressed in gliomas and functions in tumor cell adhesion. Oncogene 24, 1673-1682 (2005).
202. N. Michalski, V. Michel, A. Bahloul, G. Lefèvre, J. Barral, H. Yagi, S. Chardenoux, D.Weil, P. Martin, J. P. Hardelin, M. Sato, C. Petit, Molecular characterization of the ankle-link complex in cochlear hair cells and its role in the hair bundle functioning. J. Neurosci. 27, 6478-6488 (2007).
203. L. M. Brill, A. R. Salomon, S. B. Ficarro, M. Mukherji, M. Stettler-Gill, E. C. Peters, Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry. Anal. Chem. 76, 2763-2772 (2004).
204. S. Sui, J.Wang,B. Yang, L. Song, J. Zhang, M. Chen, J. Liu, Z. Lu, Y. Cai, S. Chen, W. Bi, Y. Zhu, F. He, X. Qian, Phosphoproteome analysis of the human Chang liver cells using SCX and a complementary mass spectrometric strategy. Proteomics 8, 2024-2034 (2008).
205. H. Molina, D. M. Horn, N. Tang, S. Mathivanan, A. Pandey, Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry. Proc. Natl. Acad. Sci. U.S.A. 104, 2199-2204 (2007).
206. R. Q. Chen, Q. K. Yang, B. W. Lu, W. Yi, G. Cantin, Y. L. Chen, C. Fearns, J. R. Yates, J. D. Lee, CDC25B mediates rapamycin-induced oncogenic responses in cancer cells. Cancer Res. 69, 2663-2668 (2009).
207. T. E. Thingholm, M. R. Larsen, C. R. Ingrell, M. Kassem, O. N. Jensen, TiO2-based phosphoproteomic analysis of the plasma membrane and the effects of phosphatase inhibitor treatment. J. Proteome Res. 7, 3304-3313 (2008).
208. H. Daub, J. V. Olsen, M. Bairlein, F. Gnad, F. S. Oppermann, R. Körner, Z. Greff, G. Kéri, O. Stemmann, M. Mann, Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol. Cell 31, 438-448 (2008).
209. F. S. Oppermann, F. Gnad, J. V. Olsen, R. Hornberger, Z. Greff, G. Kéri, M. Mann, H. Daub, Large-scale proteomics analysis of the human kinome. Mol. Cell. Proteomics 8, 1751-1764 (2009).
210. G. T. Cantin, W. Yi, B. Lu, S. K. Park, T. Xu, J. D. Lee, J. R. Yates, Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis. J. Proteome Res. 7, 1346-1351 (2008).
211. A. Guo, J. Villén, J. Kornhauser, K. A. Lee, M. P. Stokes, K. Rikova, A. Possemato, J. Nardone, G. Innocenti, R. Wetzel, Y.Wang, J. Macneill, J. Mitchell, S. P. Gygi, J. Rush, R. D. Polakiewicz, M. J. Comb, Signaling networks assembled by oncogenic EGFR and c-Met. Proc. Natl. Acad. Sci. U.S.A. 105, 692-697 (2008).
212. N. V. Popova, A. Plotnikov, I. E. Deev, A. G. Petrenko, Interaction of calcium-independent latrotoxin receptor with intracellular adapter protein TRIP8b. Dokl. Biochem. Biophys. 414, 149-151 (2007).
213. N. V. Popova, A. N. Plotnikov, R. K. Ziganshin, I. E. Deyev, A. G. Petrenko, Analysis of proteins interacting with TRIP8b adapter. Biochemistry 73, 644-651 (2008).
214. S. Hakeda-Suzuki, S. Berger-Müller, T. Tomasi, T. Usui, S. Y. Horiuchi, T. Uemura, T. Suzuki, Golden Goal collaborates with Flamingo in conferring synaptic-layer specificity in the visual system. Nat. Neurosci. 14, 314-323 (2011).
215. K. Oda, T. Shiratsuchi, H. Nishimori, J. Inazawa, H. Yoshikawa, Y. Taketani, Y. Nakamura, T. Tokino, Identification of BAIAP2 (BAI-associated protein 2), a novel human homologue of hamster IRSp53, whose SH3 domain interacts with the cytoplasmic domain of BAI1. Cytogenet. Cell Genet. 84, 75-82 (1999).
216. J. T. Koh, Z. H. Lee, K. Y. Ahn, J. K. Kim, C. S. Bae, H. H. Kim, H. J. Kee, K. K. Kim, Characterization of mouse brain-specific angiogenesis inhibitor 1 (BAI1) and phytanoyl-CoA alpha-hydroxylase-associated protein 1, a novel BAI1-binding protein. Brain Res. Mol. Brain Res. 87, 223-237 (2001).