'Eph'ective signaling: Forward, reverse and crosstalk

Journal of Cell Science

Volumn 116, Issue 14, 2003, Pages 2823-2832

  Murai, Keith K ^a,c   Pasquale, Elena B ^a,b  

^a BURNHAM INSTITUTE   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c MONTREAL GENERAL HOSPITAL   (Canada)

Author keywords

Angiogenesis; Axon guidance; Growth cone; Ras; Receptor tyrosine kinase; Rho; Synapse

Indexed keywords

EPHRIN; EPHRIN RECEPTOR; HOMEODOMAIN PROTEIN; LIGAND; LIPID; MEMBRANE PROTEIN; RAS PROTEIN; RHO FACTOR; TYROSINE KINASE RECEPTOR;

CELL ADHESION; CELL MOTION; CELL PROLIFERATION; CELL SHAPE; CELL TYPE; DIMERIZATION; HOMEOBOX; NONHUMAN; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN CONFORMATION; PROTEIN EXPRESSION; PROTEIN FAMILY; PROTEIN FUNCTION; PROTEIN INTERACTION; PROTEIN STRUCTURE; RECEPTOR BINDING; REVIEW; SIGNAL TRANSDUCTION;

ANIMALS; CELL DIVISION; CELL LINE, TUMOR; GENE EXPRESSION REGULATION; HUMANS; MODELS, BIOLOGICAL; MODELS, MOLECULAR; PHOSPHORYLATION; PROTEIN STRUCTURE, TERTIARY; RAS PROTEINS; RECEPTORS, EPH FAMILY; SIGNAL TRANSDUCTION;

EID: 0041669478     PISSN: 00219533     EISSN: None     Source Type: Journal    
DOI: 10.1242/jcs.00625     Document Type: Review

References (142)

1. Adams, R. H., Wilkinson, G. A., Weiss, C., Diella, F., Gale, N. W., Deutsch, U., Risau, W. and Klein, R. (1999). Roles of ephrinB ligands and EphB receptors in cardiovascular development: demarcation of arterial/venous domains, vascular morphogenesis, and sprouting angiogenesis. Genes Dev. 13, 295-306.
2. Adams, R. H., Diella, F., Hennig, S., Helmbacher, F., Deutsch, U. and Klein, R. (2001). The cytoplasmic domain of the ligand ephrinB2 is required for vascular morphogenesis but not cranial neural crest migration. Cell 104, 57-69.
3. Baas, P. W. and Ahmad, F. J. (2001). Force generation by cytoskeletal motor proteins as a regulator of axonal elongation and retraction. Trends Cell Biol. 11, 244-249.
4. Bar-Sagi, D. and Hall, A. (2000). Ras and Rho GTPases: a family reunion. Cell 103, 227-238.
5. Barbieri, A. M., Broccoli, V., Bovolenta, P., Alfano, G., Marchitiello, A., Mocchetti, C., Crippa, L., Bulfone, A., Marigo, V., Ballabio, A. et al. (2002). Vax2 inactivation in mouse determines alteration of the eye dorsalventral axis, misrouting of the optic fibres and eye coloboma. Development 129, 805-813.
6. Batlle, E., Henderson, J. T., Beghtel, H., van den Born, M. M., Sancho, E., Huls, G., Meeldijk, J., Robertson, J., van de Wetering, M., Pawson, T. et al. (2002). beta-Catenin and TCF mediate cell positioning in the intestinal epithelium by controlling the expression of EphB/EphrinB. Cell 111, 251-263.
7. Becker, E., Huynb-Do, U., Holland, S., Pawson, T., Daniel, T. O. and Skolnik, E. Y. (2000). Nck-interacting Ste20 kinase couples Eph receptors to c-Jun N-terminal kinase and integrin activation. Mol. Cell. Biol. 20, 1537-1545.
8. Birgbauer, E., Cowan, C. A., Sretavan, D. W. and Henkemeyer, M. (2000). Kinase independent function of EphB receptors in retinal axon pathfinding to the optic disc from dorsal but not ventral retina. Development 127, 1231-1241.
9. Borasio, G. D., John, J., Wittinghofer, A., Barde, Y. A., Sendtner, M. and Heumann, R. (1989). ras p21 protein promotes survival and fiber outgrowth of cultured embryonic neurons. Neuron 2, 1087-1096.
10. Brambilla, R., Schnapp, A., Casagranda, F., Labrador, J. P., Bergemann, A. D., Flanagan, J. G., Pasquale, E. B. and Klein, R. (1995). Membrane-bound LERK2 ligand can signal through three different Eph-related receptor tyrosine kinases. EMBO J. 14, 3116-3126.
11. Brantley, D. M., Cheng, N., Thompson, E. J., Lin, Q., Brekken, R. A., Thorpe, P. E., Muraoka, R. S., Cerretti, D. P., Pozzi, A., Jackson, D. et al. (2002). Soluble Eph A receptors inhibit tumor angiogenesis and progression in vivo. Oncogene 21, 7011-7026.
12. Brittis, P. A., Lu, Q. and Flanagan, J. G. (2002). Axonal protein synthesis provides a mechanism for localized regulation at an intermediate target. Cell 110, 223-235.
13. Bruckner, K., Pasquale, E. B. and Klein, R. (1997). Tyrosine phosphorylation of transmembrane ligands for Eph receptors. Science 275, 1640-1643.
14. Caron, E., Self, A. J. and Hall, A. (2000). The GTPase Rap1 controls functional activation of macrophage integrin alphaMbeta2 by LPS and other inflammatory mediators. Curr. Biol. 10, 974-978.
15. Carter, N., Nakamoto, T., Hirai, H. and Hunter, T. (2002). EphrinA1-induced cytoskeletal re-organization requires FAK and p130(cas). Nat. Cell Biol. 4, 565-573.
16. Chang, L. and Karin, M. (2001). Mammalian MAP kinase signalling cascades. Nature 410, 37-40.
17. Choi, S. and Park, S. (1999). Phosphorylation at Tyr-838 in the kinase domain of EphA8 modulates Fyn binding to the Tyr-615 site by enhancing tyrosine kinase activity. Oncogene 18, 5413-5422.
18. Chong, L. D., Park, E. K., Latimer, E., Friesel, R. and Daar, I. O. (2000). Fibroblast growth factor receptor-mediated rescue of x-ephrin B1-induced cell dissociation in Xenopus embryos. Mol. Cell. Biol. 20, 724-734.
19. Contractor, A., Rogers, C., Maron, C., Henkemeyer, M., Swanson, G. T. and Heinemann, S. F. (2002). Trans-synaptic Eph receptor-ephrin signaling in hippocampal mossy fiber LTP. Science 296, 1864-1869.
20. Cory, G. O. C., Garg, R., Cramer, R. and Ridley, A. J. (2002). Phosphorylation of Tyrosine 291 Enhances the Ability of WASp to Stimulate Actin Polymerization and Filopodium Formation. J. Biol. Chem. 277, 45115-45121.
21. Cowan, C. A. and Henkemeyer, M. (2001). The SH2/SH3 adaptor Grb4 transduces B-ephrin reverse signals. Nature 413, 174-179.
22. Dalva, M. B., Takasu, M. A., Lin, M. Z., Shamah, S. M., Hu, L., Gale, N. W. and Greenberg, M. E. (2000). EphB receptors interact with NMDA receptors and regulate excitatory synapse formation. Cell 103, 945-956.
23. Davy, A., Gale, N. W., Murray, E. W., Klinghoffer, R. A., Soriano, P., Feuerstein, C. and Robbins, S. M. (1999). Compartmentalized signaling by GPI-anchored ephrin-A5 requires the Fyn tyrosine kinase to regulate cellular adhesion. Genes Dev. 13, 3125-3135.
24. De Bellard, M. E., Ching, W., Gossler, A. and Bronner-Fraser, M. (2002). Disruption of segmental neural crest migration and ephrin expression in delta-1 null mice. Dev. Biol. 249, 121-130.
25. Dickson, B. J. (2001). Rho GTPases in growth cone guidance. Curr. Opin. Neurobiol. 11, 103-110.
26. Dodelet, V. C. and Pasquale, E. B. (2000). Eph receptors and ephlin ligands: embryogenesis to tumorigenesis. Oncogene 19, 5614-5619.
27. Dodelet, V. C., Pazzagli, C., Zisch, A. H., Hauser, C. A. and Pasquale, E. B. (1999). A novel signaling intermediate, SHEP1, directly couples Eph receptors to R-Ras and Rap1A. J. Biol. Chem. 274, 31941-31946.
28. Drescher, U. (2002). Eph family functions from an evolutionary perspective. Curr. Opin. Genet. Dev. 12, 397-402.
29. Durbin, L., Brennan, C., Shiomi, K., Cooke, J., Barrios, A., Shanmugalingam, S., Guthrie, B., Lindberg, R. and Holder, N. (1998). Eph signaling is required for segmentation and differentiation of the somites. Genes Dev. 12, 3096-3109.
30. Elowe, S., Holland, S. J., Kulkarni, S. and Pawson, T. (2001). Downregulation of the Ras-mitogen-activated protein kinase pathway by the EphB2 receptor tyrosine kinase is required for ephrin-induced neurite retraction. Mol. Cell. Biol. 21, 7429-7441.
31. Ethell, I. M., Irie, F., Kalo, M. S., Couchman, J. R., Pasquale, E. B. and Yamaguchi, Y. (2001). EphB/syndecan-2 signaling in dendritic spine morphogenesis. Neuron 31, 1001-1013.
32. Forcet, C., Stein, E., Pays, L., Corset, V., Llambi, F., Tessier-Lavigne, M. and Mehlen, P. (2002). Netrin-1-mediated axon outgrowth requires deleted in colorectal cancer-dependent MAPK activation. Nature 417, 443-447.
33. Freywald, A., Sharfe, N. and Roifman, C. M. (2002). The Kinase-null EphB6 Receptor Undergoes Transphosphorylation in a Complex with EphB1. J. Biol. Chem. 277, 3823-3828.
34. Gallo, G., Yee, H. F., Jr and Letourneau, P. C. (2002). Actin turnover is required to prevent axon retraction driven by endogenous actomyosin contractility. J. Cell Biol. 158, 1219-1228.
35. Gerety, S. S., Wang, H. U., Chen, Z. F. and Anderson, D. J. (1999). Symmetrical mutant phenotypes of the receptor EphB4 and its specific transmembrane ligand ephrin-B2 in cardiovascular development. Mol. Cell 4, 403-414.
36. Gerlai, R. (2001). Eph receptors and neural plasticity. Nat. Rev. Neurosci. 2, 205-209.
37. Grunwald, I. C., Korte, M., Wolfer, D., Wilkinson, G. A., Unsicker, K., Lipp, H. P., Bonhoeffer, T. and Klein, D. (2001). Kinase-independent requirement of EphB2 receptors in hippocampal synaptic plasticity. Neuron 32, 1027-1040.
38. Gu, C. and Park, S. (2001). The EphA8 receptor regulates integrin activity through p110{gamma} phosphatidylinositol-3 kinase in a tyrosine kinase activity-independent manner. Mol. Cell. Biol. 21, 4579-4597.
39. Gundersen, G. G. and Cook, T. A. (1999). Microtubules and signal transduction. Curr. Opin. Cell Biol. 11, 81-94.
40. Gurniak, C. B. and Berg, L. J. (1996). A new member of the Eph family of receptors that lacks protein tyrosine kinase activity. Oncogene 13, 777-786.
41. Halford, M. M., Armes, J., Buchert, M., Meskenaite, V., Grail, D., Hibbs, M. L., Wilks, A. F., Farlie, P. G., Newgreen, D. F., Hovens, C. M. et al. (2000). Ryk-deficient mice exhibit craniofacial defects associated with perturbed Eph receptor crosstalk. Nature Genet. 25, 414-418.
42. Han, D. C., Shen, T. L. and Guan, J. L. (2001). The Grb7 family proteins: structure, interactions with other signaling molecules and potential cellular functions. Oncogene 20, 6315-6321.
43. Han, D. C., Shen, T.-L., Miao, H., Wang, B. and Guan, J.-L. (2002). EphB1 associates with Grb7 and regulates cell migration. J. Biol. Chem. 277, 45655-45661.
44. Hattori, M., Osterfield, M. and Flanagan, J. G. (2000). Regulated cleavage of a contact-mediated axon repellent. Science 289, 1360-1365.
45. Henderson, J. T., Georgiou, J., Jia, Z. P., Robertson, J., Elowe, S., Roder, J. C. and Pawson, T. (2001). The receptor tyrosine kinase EphB2 regulates NMDA-dependent synaptic function. Neuron 32, 1041-1056.
46. Henkemeyer, M., Orioli, D., Henderson, J. T., Saxton, T. M., Roder, J., Pawson, T. and Klein, R. (1996). Nuk controls pathfinding of commissural axons in the mammalian central nervous system. Cell 86, 35-46.
47. Himanen, J. P. and Nikolov, D. B. (2003a). Eph receptors and ephrins. Int. J. Biochem. Cell Biol. 35, 130-134.
48. Himanen, J. P. and Nikolov, D. B. (2003b). Eph signaling: a structural view. Trends Neurosci. 26, 46-51.
49. Hindges, R., McLaughlin, T., Genoud, N., Henkemeyer, M. and O'Leary, D. (2002). EphB forward signaling controls directional branch extension and arborization required for dorsal-ventral retinotopic mapping. Neuron 35, 475-487.
50. Hirai, H., Maru, Y., Hagiwara, K., Nishida, J. and Takaku, F. (1987). A novel putative tyrosine kinase receptor encoded by the eph gene. Science 238, 1717-1720.
51. Hock, B., Bohme, B., Karn, T., Yamamoto, T., Kaibuchi, K., Holtrich, U., Holland, S., Pawson, T., Rubsamen-Waigmann, H. and Strebhardt, K. (1998). PDZ-domain-mediated interaction of the Eph-related receptor tyrosine kinase EphB3 and the ras-binding protein AF6 depends on the kinase activity of the receptor. Proc. Natl. Acad. Sci. USA 95, 9779-9784.
52. Holland, S. J., Gale, N. W., Mbamalu, G., Yancopoulos, G. D., Henkemeyer, M. and Pawson, T. (1996). Bidirectional signalling through the EPH-family receptor Nuk and its transmembrane ligands. Nature 383, 722-725.
53. Holland, S. J., Gale, N. W., Gish, G. D., Roth, R. A., Songyang, Z., Cantley, L. C., Henkemeyer, M., Yancopoulos, G. D. and Pawson, T. (1997). Juxtamembrane tyrosine residues couple the Eph family receptor EphB2/Nuk to specific SH2 domain proteins in neuronal cells. EMBO J 16, 3877-3888.
54. Holmberg, J. and Frisen, J. (2002). Ephrins are not only unattractive. Trends Neurosci. 25, 239-243.
55. Huai, J. and Drescher, U. (2001). An ephrin-A-dependent signaling pathway controls integrin function and is linked to the tyrosine phosphorylation of a 120-kDa protein. J. Biol. Chem. 276, 6689-6694.
56. Hussain, N. K., Yamabhai, M., Ramjaun, A. R., Guy, A. M., Baranes, D., O'Bryan, J. P., Der, C. J., Kay, B. K. and McPherson, P, S. (1999). Splice variants of intersectin are components of the endocytic machinery in neurons and nonneuronal cells. J. Biol. Chem. 274, 15671-15677.
57. Huynh-Do, U., Stein, E., Lane, A. A., Liu, H., Cerretti, D. P. and Daniel, T. O. (1999). Surface densities of ephrin-B1 determine EphB1-coupled activation of cell attachment through alphavbeta3 and alpha5beta1 integrins. EMBO J. 18, 2165-2173.
58. Huynh-Do, U., Vindis, C., Liu, H., Cerretti, D. P., McGrew, J. T., Enriquez, M., Chen, J. and Daniel, T. O. (2002). Ephrin-B1 transduces signals to activate integrin-mediated migration, attachment and angiogenesis. J. Cell Sci. 115, 3073-3081.
59. Irie, F. and Yamaguchi, Y. (2002). EphB receptors regulate dendritic spine development via intersectin, Cdc42 and N-WASP. Nat. Neurosci. 5, 1117-1118.
60. Johnson, G. L. and Lapadat, R. (2002). Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science 298, 1911-1912.
61. Jones, N. and Dumont, D. J. (1999). Recruitment of Dok-R to the EGF receptor through its PTB domain is required for attenuation of Erk MAP kinase activation. Curr. Biol. 9, 1057-1060.
62. Jurney, W. M., Gallo, G., Letourneau, P. C. and McLoon, S. C. (2002). Rac1-mediated endocytosis during Ephrin-A2- and Semaphorin 3A-induced growth cone collapse. J. Neurosci. 22, 6019-6028.
63. Kalo, M. S. and Pasquale, E. B. (1999). Signal transfer by Eph receptors. Cell Tissue Res. 298, 1-9.
64. Kalo, M. S., Yu, H. H. and Pasquale, E. B. (2001). In vivo tyrosine phosphorylation sites of activated ephrin-B1 and EphB2 from neural tissue. J. Biol. Chem. 276, 38940-38948.
65. Karam, S. D., Burrows, R. C., Logan, C., Koblar, S., Pasquale, E. B. and Bothwell, M. (2000). Eph receptors and ephrins in the developing chick cerebellum: relationship to sagittal patterning and granule cell migration. J. Neuroscience 20, 6488-6500.
66. Katso, R. M., Russell, R. B. and Ganesan, T. S. (1999). Functional analysis of H-Ryk, an atypical member of the receptor tyrosine kinase family. Mol. Cell. Biol. 19, 6427-6440.
67. Kim, I., Ryu, Y. S., Kwak, H. J., Ahn, S. Y., Oh, J. L., Yancopoulos, G. D., Gale, N. W. and Koh, G. Y. (2002). EphB ligand, ephrinB2, suppresses the VEGF- and angiopoietin 1-induced Ras/mitogen-activated protein kinase pathway in venous endothelial cells. FASEB J. 16, 1126-1128.
68. Klemke, R. L., Cai, S., Giannini, A. L., Gallagher, P. J., de Lanerolle, P. and Cheresh, D. A. (1997). Regulation of cell motility by mitogen-activated protein kinase. J. Cell Biol. 137, 481-492.
69. Kong, H. Y., Boulter, J., Weber, J. L., Lai, C. and Chao, M. V. (2001). An evolutionarily conserved transmembrane protein that is a novel downstream target of neurotrophin and ephrin receptors. J. Neurosci. 21, 176-185.
70. Koolpe, M., Dail, M. and Pasquale, E. B. (2002). An ephrin mimetic peptide that selectively targets the EphA2 receptor. J. Biol. Chem. 277, 46974-46979.
71. Koshiba-Takeuchi, K., Takeuchi, J. K., Matsumoto, K., Momose, T., Uno, K., Hoepker, V., Ogura, K., Takahashi, N., Nakamura, H., Yasuda, K. et al. (2000). Tbx5 and the retinotectum projection. Science 287, 134-137.
72. Kozma, R., Sarner, S., Ahmed, S. and Lim, L. (1997). Rho family GTPases and neuronal growth cone remodelling: relationship between increased complexity induced by Cdc42Hs, Rac1, and acetylcholine and collapse induced by RhoA and lysophosphatidic acid. Mol. Cell. Biol. 17, 1201-1211.
73. Krull, C. E., Lansford, R., Gale, N. W., Collazo, A., Marcelle, C., Yancopoulos, G. D., Fraser, S. E. and Bronner-Fraser, M. (1997). Interactions of Eph-related receptors and ligands confer rostrocaudal pattern to trunk neural crest migration. Curr. Biol. 7, 571-580.
74. Kullander, K. and Klein, R. (2002). Mechanisms and functions of Eph and ephrin signalling. Nat. Rev. Mol. Cell Biol. 3, 475-486.
75. Kullander, K., Mather, N. K., Diella, F., Dottori, M., Boyd, A. W. and Klein, R. (2001). Kinase-dependent and kinase-independent functions of EphA4 receptors in major axon tract formation in vivo. Neuron 29, 73-84.
76. Lai, K. O., Ip, F. C. F., Cheung, J., Fu, A. K. Y. and Ip, N. Y. (2001). Expression of Eph receptors in skeletal muscle and their localization at the neuromuscular junction. Mol. Cell. Neurosci. 17, 1034-1047.
77. Lawrenson, I. D., Wimmer-Kleikamp, S. H., Lock, P., Schoenwaelder, S. M., Down, M., Boyd, A. W., Alewood, P. F. and Lackmann, M. (2002). Ephrin-A5 induces rounding, blebbing and de-adhesion of EphA3-expressing 293T and melanoma cells by CrkII and Rho-mediated signalling. J. Cell Sci. 115, 1059-1072.
78. Leblanc, V., Tocque, B. and Delumeau, I. (1998). Ras-GAP controls Rho-mediated cytoskeletal reorganization through its SH3 domain. Mol. Cell. Biol. 18, 5567-5578.
79. Logan, C., Wizenmann, A., Drescher, U., Monschau, B., Bonhoeffer, F. and Lumsden, A. (1996). Rostral optic tectum acquires caudal characteristics following ectopic engrailed expression. Curr. Biol. 6, 1006-1014.
80. Lu, Q., Sun, E. E., Klein, R. S. and Flanagan, J. G. (2001). Ephrin-B reverse signaling is mediated by a novel PDZ-RGS protein and selectively inhibits G protein-coupled chemoattraction. Cell 105, 69-79.
81. Luo, H. Y., Wan, X. C., Wu, Y. L. and Wu, J. P. (2001). Cross-linking of EphB6 resulting in signal transduction and apoptosis in Jurkat cells. J. Immunol. 167, 1362-1370.
82. Luo, H., Yu, G., Wu, Y. and Wu, J. (2002). EphB6 crosslinking results in costimulation of T cells. J. Clin. Invest. 110, 1141-1150.
83. Luo, L. (2000). Rho GTPases in neuronal morphogenesis. Nat. Rev. Neurosci. 1, 173-180.
84. Mann, F., Ray, S., Harris, W. and Holt, C. (2002). Topographic mapping in dorsoventral axis of the xenopus retinotectal system depends on signaling through Ephrin-B ligands. Neuron 35, 461-473.
85. Manning, G., Plowman, G. D., Hunter, T. and Sudarsanam, S. (2002). Evolution of protein kinase signaling from yeast to man. Trends Biochem. Sci. 27, 514-520.
86. Matsuoka, H., Iwata, N., Ito, M., Shimoyama, M., Nagata, A., Chihara, K., Takai, S. and Matsui, T. (1997). Expression of a kinase-defective Eph-like receptor in the normal human brain. Biochem. Biophys. Res. Commun. 235, 487-492.
87. Meima, L., Kljavin, I. J., Moran, P., Shih, A., Winslow, J. W. and Caras, I. W. (1997a). AL-1-induced growth cone collapse of rat cortical neurons is correlated with REK7 expression and rearrangement of the actin cytoskeleton. Eur. J. Neurosci. 9, 177-188.
88. Meima, L., Moran, P., Matthews, W. and Caras, I. W. (1997b). Lerk2 (ephrin-B1) is a collapsing factor for a subset of cortical growth cones and acts by a mechanism different from AL-1 (ephrin-A5). Mol. Cell. Neurosci. 9, 314-328.
89. Mellitzer, G., Xu, Q. L. and Wilkinson, D. G. (1999). Eph receptors and ephrins restrict cell intermingling and communication. Nature 400, 77-81.
90. Miao, H., Burnett, E., Kinch, M., Simon, E. and Wang, B. (2000). Activation of EphA2 kinase suppresses integrin function and causes focal-adhesion-kinase dephosphorylation. Nat. Cell Biol. 2, 62-69.
91. Miao, H., Wei, B. R., Peehl, D. M., Li, Q., Alexandrou, T., Schelling, J. R., Rhim, J. S., Sedor, J. R., Burnett, E. and Wang, B. C. (2001). Activation of EphA receptor tyrosine kinase inhibits the Ras/MAPK pathway. Nat. Cell Biol. 3, 527-530.
92. Mui, S. H., Hindges, R., O'Leary, D. D. M., Lemke, G. and Bertuzzi, S. (2002). The homeodomain protein Vax2 patterns the dorsoventral and nasotemporal axes of the eye. Development 129, 797-804.
93. Mukouyama, Y. S., Shin, D., Britsch, S., Taniguchi, M. and Anderson, D. J. (2002). Sensory nerves determine the pattern of arterial differentiation and blood vessel branching in the skin. Cell 109, 693-705.
94. Murai, K. K. and Pasquale, E. B. (2002). Can Eph receptors stimulate the mind? Neuron 33, 159-162.
95. Murai, K. K., Nguyen, L. N., Irie, F., Yamaguchi, Y. and Pasquale, E. B. (2003). Control of hippocampal dendritic spine morphology through ephrin-A3/EphA4 signaling. Nat. Neurosci. 6, 153-160.
96. Nagashima, K., Endo, A., Ogita, H., Kawana, A., Yamagishi, A., Kitabatake, A., Matsuda, M. and Mochizuki, N. (2002). Adaptor Protein Crk Is Required for Ephrin-B1-induced Membrane Ruffling and Focal Complex Assembly of Human Aortic Endothelial Cells. Mol. Biol. Cell 13, 4231-4242.
97. Nobes, C. D. and Hall, A. (1995). Rho, rac, and cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia. Cell 81, 53-62.
98. Ogawa, K., Pasqualini, R., Lindberg, R. A., Kain, R., Freeman, A. L. and Pasquale, E. B. (2000). The ephrin-A1 ligand and its receptor, EphA2, are expressed during tumor neovascularization. Oncogene 19, 6043-6052.
99. Orsulic, S. and Kemler, R. (2000). Expression of Eph receptors and ephrins is differentially regulated by E-cadherin. J. Cell Sci. 113, 1793-1802.
100. Palmer, A., Zimmer, M., Erdmann, K. S., Eulenburg, V., Porthin, A., Heumann, R., Deutsch, U. and Klein, R. (2002). EphrinB phosphorylation and reverse signaling: regulation by Src kinases and PTP-BL phosphatase. Mol. Cell 9, 725-737.
101. Pandey, A., Lazar, D. F., Saltiel, A. R. and Dixit, V. M. (1994). Activation of the Eck receptor protein tyrosine kinase stimulates phosphatidylinositol 3-kinase activity. J. Biol. Chem. 269, 30154-30157.
102. Pandey, A., Shao, H., Marks, R. M., Polverini, P. J. and Dixit, V. M. (1995). Role of B61, the ligand for the Eck receptor tyrosine kinase, in TNF-alpha-induced angiogenesis. Science 268, 567-569.
103. Pasini, A. and Wilkinson, D. G. (2002). Stabilizing the regionalisation of the developing vertebrate central nervous system. Bioessays 24, 427-438.
104. Penzes, P., Beeser, A., Chernoff, J., Schiller, M. R., Eipper, B. A., Mains, R. E. and Huganir, R. L. (2003). Rapid Induction of Dendritic Spine Morphogenesis by trans-Synaptic EphrinB-EphB receptor activation of the Rho-GEF kalirin. Neuron 37, 263-274.
105. Pratt, R. L. and Kinch, M. S. (2002). Activation of the EphA2 tyrosine kinase stimulates the MAP/ERK kinase signaling cascade. Oncogene 21, 7690-7699.
106. Prevost, N., Woulfe, D., Tanaka, T. and Brass, L. F. (2002). Interactions between Eph kinases and ephrins provide a mechanism to support platelet aggregation once cell-to-cell contact has occurred. Proc. Natl. Acad. Sci. USA 99, 9219-9224.
107. Reedquist, K. A., Ross, E., Koop, E. A., Wolthuis, R. M. F., Zwartkruis, F. J. T., van Kooyk, Y., Salmon, M., Buckley, C. D. and Bos, J. L. (2000). The Small GTPase, Rap1, Mediates CD31-induced Integrin Adhesion. J. Cell Biol. 148, 1151-1158.
108. Sakakibara, A. and Hattori, S. (2000). Chat, a Cas/HEF1-associated adaptor protein that integrates multiple signaling pathways. J. Biol. Chem. 275, 6404-6410.
109. Sakakibara, A., Ohba, Y., Kurokawa, K., Matsuda, M. and Hattori, S. (2002). Novel function of Chat in controlling cell adhesion via Cas-Crk-C3G-pathway-mediated Rap1 activation. J. Cell Sci. 115, 4915-4924.
110. Sanders, L. C., Matsumura, F., Bokoch, G. M. and de Lanerolle, P. (1999). Inhibition of myosin light chain kinase by p21-activated kinase. Science 283, 2083-2085.
111. Santiago, A. and Erickson, C. A. (2002). Ephrin-B ligands play a dual role in the control of neural crest cell migration. Development 129, 3621-3632.
112. Schulte, D. and Cepko, C. L. (2000). Two homeobox genes define the domain of EphA3 expression in the developing chick retina. Development 127, 5033-5045.
113. Shamah, S. M., Lin, M. Z., Goldberg, J. L., Estrach, S., Sahin, M., Hu, L., Bazalakova, M., Neve, R. L., Corfas, G., Debant, A. et al. (2001). EphA receptors regulate growth cone dynamics through the novel guanine nucleotide exchange factor ephexin. Cell 105, 233-244.
114. Smith, A., Robinson, V., Patel, K. and Wilkinson, D. G. (1997). The EphA4 and EphB1 receptor tyrosine kinases and ephrin-B2 ligand regulate targeted migration of branchial neural crest cells. Curr. Biol. 7, 561-570.
115. Song, J., Vranken, W., Xu, P., Gingras, R., Noyce, R. S., Yu, Z., Shen, S. H. and Ni, F. (2002). Solution structure and backbone dynamics of the functional cytoplasmic subdomain of human ephrin B2, a cell-surface ligand with bidirectional signaling properties. Biochemistry 41, 10942-10949.
116. Stadler, H. S., Higgins, K. M. and Capecchi, M. R. (2001). Loss of Eph-receptor expression correlates with loss of cell adhesion and chondrogenic capacity in Hoxa13 mutant limbs. Development 128, 4177-4188.
117. Stein, E., Cerretti, D. P. and Daniel, T. O. (1996). Ligand activation of ELK receptor tyrosine kinase promotes its association with Grb10 and Grb2 in vascular endothelial cells. J. Biol. Chem. 271, 23588-23593.
118. Stein, E., Huynh-Do, U., Lane, A. A., Cerretti, D. P. and Daniel, T. O. (1998a). Nck recruitment to Eph receptor, EphB1/ELK, couples ligand activation to c-Jun kinase. J. Biol. Chem. 273, 1303-1308.
119. Stein, E., Lane, A. A., Cerretti, D. P., Schoecklmann, H. O., Schroff, A. D., Van Etten, R. L. and Daniel, T. O. (1998b). Eph receptors discriminate specific ligand oligomers to determine alternative signaling complexes, attachment, and assembly responses. Genes Dev. 12, 667-678.
120. Steinle, J. J., Meininger, C. J., Forough, R., Wu, G., Wu, M. H. and Granger, H. J. (2002). Eph B4 receptor signaling mediates endothelial cell migration and proliferation via the phosphatidylinositol 3-kinase pathway. J. Biol. Chem. 277, 43830-43835.
121. Suenobu, S., Takakura, N., Inada, T., Yamada, Y., Yuasa, H., Zhang, X. Q., Sakano, S., Oike, Y. and Suda, T. (2002). A role of EphB4 receptor and its ligand, ephrin-B2, in erythropoiesis. Biochem. Biophys. Res. Commun. 293, 1124-1131.
122. Takasu, M. A., Dalva, M. B., Zigmond, R. E. and Greenberg, M. E. (2002). Modulation of NMDA receptor-dependent calcium influx and gene expression through EphB receptors. Science 295, 491-495.
123. Theil, T., Frain, M., Gilardi-Hebenstreit, P., Flenniken, A., Charnay, P. and Wilkinson, D. G. (1998). Segmental expression of the EphA4 (Sek-1) receptor tyrosine kinase in the hindbrain is under direct transcriptional control of Krox-20. Development 125, 443-452.
124. Tong, J., Elowe, S., Nash, P. and Pawson, T. (2003). Manipulation of EphB2 regulatory motifs and SH2 binding sites switches MAPK signaling and biological activity. J. Biol. Chem. 278, 6111-6119.
125. Trivier, E. and Ganesan, T. S. (2002). RYK, a Catalytically Inactive Receptor Tyrosine Kinase, Associates with EphB2 and EphB3 but Does Not Interact with AF-6. J. Biol. Chem. 277, 23037-23043.
126. Wahl, S., Barth, H., Ciossek, T., Aktories, K. and Mueller, B. K. (2000). Ephrin-A5 induces collapse of growth cones by activating Rho and Rho kinase. J. Cell Biol. 149, 263-270.
127. Walker-Daniels, J., Riese, D. J., 2nd and Kinch, M. S. (2002). c-Cbl-dependent EphA2 protein degradation is induced by ligand binding. Mol. Cancer Res. 1, 79-87.
128. Wang, H. U. and Anderson, D. J. (1997). Eph family transmembrane ligands can mediate repulsive guidance of trunk neural crest migration and motor axon outgrowth. Neuron 18, 383-396.
129. Wang, H. U., Chen, Z. F. and Anderson, D. J. (1998). Molecular distinction and angiogenic interaction between embryonic arteries and veins revealed by ephrin-B2 and its receptor Eph-B4. Cell 93, 741-753.
130. Wang, X., Roy, P. J., Holland, S. J., Zhang, L. W., Culotti, J. G. and Pawson, T. (1999). Multiple ephrins control cell organization in C. elegans using kinase-dependent and -independent functions of the VAB-1 Eph receptor. Mol. Cell 4, 903-913.
131. Wang, Y., Ota, S., Kataoka, H., Kanamori, M., Li, Z., Band, H., Tanaka, M. and Sugimura, H. (2002a). Negative regulation of EphA2 receptor by Cbl. Biochem. Biophys. Res. Commun. 296, 214-220.
132. Wang, Z., Miura, N., Bonelli, A., Mole, P., Carlesso, N., Olson, D. P. and Scadden, D. T. (2002b). Receptor tyrosine kinase, EphB4 (HTK), accelerates differentiation of select human hematopoietic cells. Blood 99, 2740-2747.
133. Wilkinson, D. G. (2001). Multiple roles of Eph receptors and ephrins in neural development. Nat. Rev. Neurosci. 2, 155-164.
134. Wybenga-Groot, L. E., Baskin, B., Ong, S. H., Tong, J. F., Pawson, T. and Sicheri, F. (2001). Structural basis for autoinhibition of the EphB2 receptor tyrosine kinase by the unphosphorylated juxtamembrane region. Cell 106, 745-757.
135. Xu, Q., Mellitzer, G., Robinson, V. and Wilkinson, D. G. (1999). In vivo cell sorting in complementary segmental domains mediated by Eph receptors and ephrins. Nature 399, 267-271.
136. Yu, H. H., Zisch, A. H., Dodelet, V. C. and Pasquale, E. B. (2001). Multiple signaling interactions of Ab1 and Arg kinases with the EphB2 receptor. Oncogene 20, 3995-4006.
137. Yuan, X. B., Jin, M., Xu, X., Song, Y. Q., Wu, C. P., Poo, M. M. and Duan, S. (2003). Signalling and crosstalk of Rho GTPases in mediating axon guidance. Nat. Cell Biol. 5, 38-45.
138. Yuasa, J., Hirano, S., Yamagata, M. and Noda, M. (1996). Visual projection map specified by topographic expression of transcription factors in the retina. Nature 382, 632-635.
139. Zhang, Z., Vuori, K., Wang, H., Reed, J. C. and Ruoslahti, E. (1996). Integrin activation by R-ras. Cell 85, 61-69.
140. Zisch, A. H., Kalo, M. S., Chong, L. D. and Pasquale, E. B. (1998). Complex formation between EphB2 and Src requires phosphorylation of tyrosine 611 in the EphB2 juxtamembrane region. Oncogene 16, 2657-2670.
141. Zisch, A. H., Pazzagli, C., Freeman, A. L., Schneller, M., Hadman, M., Smith, J. W., Ruoslahti, E. and Pasquale, E. B. (2000). Replacing two conserved tyrosines of the EphB2 receptor with glutamic acid prevents binding of SH2 domains without abrogating kinase activity and biological responses. Oncogene 19, 177-187.
142. Zou, J. X., Wang, B., Kalo, M. S., Zisch, A. H., Pasquale, E. B. and Ruoslahti, E. (1999). An Eph receptor regulates integrin activity through R-Ras. Proc. Natl. Acad. Sci. USA 96, 13813-13818.