Signaling by Eph receptors and their ephrin ligands

Current Opinion in Neurobiology

Volumn 8, Issue 3, 1998, Pages 375-382

  Brückner, Katja ^a   Klein, Rüdiger ^a  

^a EUROPEAN MOLECULAR BIOLOGY LABORATORY   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ACTIN; LIGAND; PROTEIN TYROSINE KINASE;

CELL MIGRATION; CYTOSKELETON; NERVE FIBER; NONHUMAN; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION;

EID: 0032103082     PISSN: 09594388     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0959-4388(98)80064-0     Document Type: Article

References (91)

1. Unified nomenclature for Eph family receptors and their ligands, the ephrins. of special interest Cell. 90:1997;403 Official agreement on a new simplified nomenclature for Eph receptors and their ligands.
2. Orioli D, Klein R. The Eph receptor family: axonal guidance by contact repulsion. Trends Genet. 13:1997;354-359.
3. Davis S, Gale NW, Aldrich TH, Maisonpierre PC, Lhotak V, Pawson T, Goldfarb M, Yancopoulos GD. Ligands for EPH-related receptor tyrosine kinases that require membrane attachment or clustering for activity. Science. 266:1994;816-819.
4. Drescher U. The Eph family in the patterning of neural development. Curr Biol. 7:1997;R799-R807.
5. Flanagan JG, Vanderhaeghen P. The ephrins and Eph receptors in neural development. Annu Rev Neurosci. 21:1998;309-345.
6. Robinson V, Smith A, Flenniken AM, Wilkinson DG. Roles ofEph receptors and ephrins in neural crest pathfinding. Cell Tissue Res. 290:1997;265-274.
7. Pandey A, Shao H, Marks RM, Polverini PJ, Dixit VM. Role of B61, the ligand for the Eck receptor tyrosine kinase, in TNF-α-induced angiogenesis. Science. 265:1995;567-569.
8. Stein E, Lane AA, Ceretti DP, Schoecklmann HO, Schroff AD, VanEtten RL, Daniel TO. Eph receptors discriminate specific ligand oligomers to determine alternative signaling complexes, attachment and assembly responses. of outstanding interest Genes Dev. 12:1998;667-678 The authors demonstrate that depending on the state of ephrin multimerization, differential Eph receptor signaling complexes and biological effects are induced. This is the first report on LMW-PTP in Eph signal transduction.
9. Gale NW, Holland SJ, Valenzuela DM, Flenniken A, Pan L, Ryan TE, Henkemeyer M, Strebhardt K, Hirai H, Wilkinson DG, et al. Eph receptors and ligands comprise two major specificity subclasses and are reciprocally compartmentalized during embryogenesis. Neuron. 17:1996;9-19.
10. Meima L, Kljavin IJ, Moran P, Shih A, Winslow JW, Caras IW. AL-1 induced growth cone collapse of rat cortical neurons is correlated with REK7 expression and rearrangement of the actin cytoskeleton. Eur J Neurosci. 9:1996;177-188.
11. Holland SJ, Gale NW, Gish GD, Roth RA, Songyang Z, Cantley LC, Henkemeyer M, Yancopoulos GD, Pawson T. Juxtamembrane tyrosine residues couple the Eph family receptor EphB2/Nuk to specific SH2 domain proteins in neuronal cells. of outstanding interest EMBO J. 16:1997;3877-3888 This paper describes the identification of EphB2-activated signaling pathways that involve proteins that control the cytoskeletal architecture and that potentially represent mediators of axon pathfinding.
12. Tanaka E, Sabry J. Making the connection: cytoskeletal rearrangements during growth cone guidance. Cell. 83:1995;171-176.
13. Fan J, Raper JA. Localized collapsing cues can steer growth cones without inducing their full collapse. Neuron. 14:1995;263-274.
14. Schlessinger J, Ulrich A. Growth factor signaling by receptor tyrosine kinases. Neuron. 9:1992;383-391.
15. Labrador JP, Brambilla R, Klein R. The N-terminal globular domain of Eph receptors is sufficient for ligand binding and receptor signaling. of special interest EMBO J. 16:1997;3889-3897 This study determined the first structural elements involved in the ligand - receptor interaction. An amino-terminal region of unknown structure confers specific ligand binding on receptors of both subclasses.
16. Pawson T. Protein modules and signaling networks. Nature. 373:1995;573-580.
17. Pawson T, Scott JD. Signaling through scaffold, anchoring, and adaptor proteins. of outstanding interest Science. 278:1997;2075-2080 This review discusses the role of scaffold, anchoring and adaptor proteins in recruiting active anzymes into signaling pathways as part of regulatory mechanisms to spatially organize the process of signal transduction.
18. Van der Geer P, Hunter T, Lindberg RA. Receptor protein - tyrosine kinases and their signal transduction pathways. Annu Rev Cell Biol. 10:1994;251-337.
19. Brambilla R, Klein R. Telling axons where to grow: a role for Eph receptor tyrosine kinases in guidance. Mol Cell Neurosci. 6:1995;487-495.
20. Ellis C, Kasmi F, Ganju P, Walis E, Panayotou G, Reith AD. A juxtamembrane autophosphorylation site in the Eph family receptor tyrosine kinase, Sek, mediates high affinity interaction with p59fyn. of outstanding interest Oncogene. 12:1996;1727-1736 The first report on a Src kinase interacting with an Eph receptor and the identification of two major autophosphorylation sited in the juxtamembrane region.
21. Zisch AH, Kalo MS, Chong LD, Pasquale EB. Complex formation between EphB2 and Src requires phosphorylation of tyrosine 611 in the EphB2 juxtamembrane region. Oncogene. 1998;. in press.
22. McGlade J, Brunkhorst B, Anderson D, Mbamalu G, Settleman J, Dedhar S, Rozakis-Adcock M, Bo Chen L, Pawson T. The N-terminal region of GAP regulates cytoskeletal structure and cell adhesion. EMBO J. 12:1993;3073-3081.
23. Chant J, Stowers L. GTPase cascades choreographing cellular behavior: movement, morphogenesis, and more. Cell. 81:1995;1-4.
24. Hall A. Rho GTPases and the actin cytoskeleton. of outstanding interest Science. 279:1998;509-514 The most recent review on the role of Rho GTPases in controlling the actin cytoskeleton of different cell types, including neurons. Progress in identifying upstream activators and downstream targets, and genetic model systems are discussed.
25. Nobes CD, Hall A. Rho,Rac, and Cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia. Cell. 81:1995;53-62.
26. Mackay DJG, Nobes CD, Hall A. The Rho's progress: a potential role during neuritogenesis for the Rho family of GTPases. Trends Neurosci. 18:1995;496-501.
27. Luo L, Liao J, Jan LY, Jan YN. Distinct morphogenetic functions of similar small GTPases: Drosophila Drac1 is involved in axonal outgrowth and myoblast fusion. Genes Dev. 8:1994;1787-1802.
28. Kozma R, Sarner S, Ahmed S, Lim L. Rho family GTPases and neuronal growth cone remodeling: relationship between increased complexity induced by Cdc42Hs, Rac1, and acetylcholine and collapse induced by RhoA and lysophosphatidic acid. Mol Cell Biol. 17:1997;1201-1211.
29. dok: a constitutively tyrosine-phosphorylated GAP-associated protein in chronic myelogenous leukemia progenitor cells. Cell. 88:1997;197-204.
30. Yamanashi Y, Baltimore D. Identification of the AbI- and rasGAP-associated 62kDa protein as a docking protein, Dok. Cell. 88:1997;205-211.
31. Neet K, Hunter T. The nonreceptor protein - tyrosine kinase CSK complexes directly with the GTPase-activating protein-associated p62 protein in cells expressing v-Src or activated c-Src. Mol Cell Biol. 15:1995;4908-4920.
32. Tang J, Feng G-S, Li W. Induced direct binding of the adaptor protein Nck to the GTPase-activating protein-associated protein p62 by epidermal growth factor. Oncogene. 15:1997;1823-1832.
33. of outstanding interest Stein E, Huynh-Do U, Lane AA, Ceretti DP, Daniel TD. Nck recruitment to Eph receptor, EphB1/Elk, couples ligand activation to c-Jun kinase. of special interest J Biol Chem. 273:1998;1303-1308 This study suggests direct recruitment of Nck by activated EphB1, an alternative way to the described p62dok-mediated Nck binding in EphB2 signal transduction [11].
34. Garrity PA, Rao Y, Salecker I, McGlade J, Pawson T, Zipursky SL. Drosophila photoreceptor axon guidance and targeting requires the dreadlocks SH2/SH3 adapter protein. of special interest Cell. 85:1996;639-650 A genetic study showing that dock (Nck) is required for photoreceptor cell axon guidance and targeting. It is proposed that dock transmits signals in the growth cone in response to guidance and targeting cues.
35. Lu W, Katz S, Gupta R, Mayer BJ. Activation of Pak by membrane localization mediated by an SH3 domain from the adaptor protein Nck. Curr Biol. 7:1997;85-94.
36. Rivero-Lezcano OM, Marcilla A, Sameshima JH, Robbins KC. Wiskott-Aldrich Syndrome protein physically associates with Nck through Src homology 3 domains. Mol Cell Biol. 15:1995;5725-5731.
37. Bagrodia S, Taylor SJ, Creasy CL, Chernoff J, Cerione RA. Identification of a mouse p21Cdc42/Rac activated kinase. J Biol Chem. 270:1995;22731-22737.
38. Chou MM, Hanafusa H. A novel ligand for SH3 domains. J Biol Chem. 270:1995;7359-7364.
39. Hu Q, Milfay D, Williams LT. Binding of NCK to SOS and activation of ras-dependent gene expression. Mol Cell Biol. 15:1995;1169-1174.
40. Manser E, Leung T, Salihuddin H, Zhao Z-S, Lim L. A brain serine/threonine protein kinase activated by Cdc42 and Rac1. Nature. 367:1994;40-46.
41. Symons M, Derry JMJ, Karlak B, Jiang S, Lemahieu V, McCormick F, Francke U, Abo A. Wiskott-Aldrich Syndrome protein, a novel effector for the GTPase CDC42Hs, is implicated in actin polymerisation. Cell. 84:1996;723-734.
42. Kolluri R, Fuchs Tolias K, Carpenter CL, Rosen FS, Kirchhausen T. Direct interaction of the Wiskott-Aldrich Syndrome protein with the GTPase Cdc42. Proc Natl Acad Sci USA. 93:1996;5615-5618.
43. Appenström P, Lindberg U, Hall A. Two GTPases, Cdc42 and Rac, bind directly to a protein implicated in the immunodeficiency disorder Wiskott - Aldrich Syndrome. Curr Biol. 6:1995;70-75.
44. Lim L, Manser E, Leung T, Hall C. Regulation of phosphorylation pathways by p21 GTPases. Eur J Biochem. 242:1996;171-185.
45. Manser E, Huang H-Y, Loo T-H, Chen X-Q, Dong J-M, Leung T, Lim L. Expression of constitutively active α-PAK reveals effects of the kinase on actin and focal complexes. Mol Cell Biol. 17:1997;1129-1143.
46. Li R. Bee1, a yeast protein with homology to Wiskott-Aldrich Syndrome protein, is critical for the assembly of cortical actin cytoskeleton. J Cell Biol. 136:1997;649-658.
47. Miki H, Sasaki T, Takai Y, Takenawa T. Induction of filopodium by a WASP-related actin-depolymerizing protein N-WASP. of special interest Nature. 391:1998;93-96 The authors report that N-WASP but not WASP is an effector of Cdc42 in the formation of filopodia.
48. Erpel T, Courtneidge SA. Src family protein tyrosine kinases and cellular signal transduction pathways. Curr Opin Cell Biol. 7:1995;176-182.
49. Thomas SM, Soriano P, Imamoto A. Specific and redundant roles of Src and Fyn in organizing the cytoskeleton. Nature. 376:1995;267-271.
50. Boyer B, Roche S, Denoyelle M, Thiery JP. Src and Ras are involved in separate pathways in epithelial cell scattering. EMBO J. 16:1997;5904-5913.
51. Henkemeyer M, Marengere LEM, McGlade J, Olivier JP, Conion RA, Holmyard DP, Letwin K, Pawson T. Immunolocalization of the Nuk receptor tyrosine kinase suggests role in segmental patterning of the brain and axonogenesis. Oncogene. 9:1994;1001-1014.
52. Zhan X, Plourde C, Hu X, Friesel R, Maciag T. Association of fibroblast growth factor receptor-1 with c-Src correlates with association between c-Src and cortactin. J Biol Chem. 269:1994;20221-20224.
53. Maa M-C, Wilson LK, Moyers JS, Vines RR, Parsons JT, Parsons SJ. Identification and characterization of a cytoskeleton-associated, epidermal growth factor sensitive pp60c-src substrate. Oncogene. 7:1992;2429-2438.
54. Huang C, Ni Y, Wang T, Gao Y, Haudenschild CC, Zhan X. Down-regulation of the filamentous actin cross-linking activity of cortactin by Src-mediated tyrosine phosphorylation. of special interest J Biol Chem. 272:1997;13911-13915 This study presents interesting data on Src being able to regulate the activity of its substrate, cortactin, towards the cytoskeleton and suggests a role for cortactin as an F-actin modulator in Src-mediated cytoskeleton reorganization.
55. Banin S, Truong O, Katz DR, Waterfield MD, Brickell PM, Gout I. Wiskott - Aldrich Syndrome protein (WASp) is a binding partner for c-Src family protein-tyrosine kinases. Curr Biol. 6:1996;981-988.
56. Stein E, Cerretti P, Danial TO. Ligand activation of ELK receptor tyrosine kinase promotes its association with Grb10 and Grb2 in vascular endothelial cells. of special interest J Biol Chem. 271:1996;23588-23593 The identification of two substrates for Eph receptors, the biochemical characterization of their interaction with receptors is described.
57. Ooi J, Yajnik V, Immanuel D, Gordon M, Moskow JJ, Buchberg AM, Margolis B. The cloning of Grb10 reveals a new family of SH2 domain proteins. Oncogene. 10:1995;1621-1630.
58. Manser J, Roonprapunt C, Margolis B. C. elegans cell migration gene mig-10 shares similarities with a family of SH2 domain proteins and acts nonautonomously in excretory canal development. Dev Biol. 184:1997;150-164.
59. Matuoka K, Shibasaki F, Shibata M, Takenawa T. Ash/Grb2, a SH2/SH3-containing protein, couples to signaling for mitogenesis and cytoskeletal reorganization by EGF and PDGF. EMBO J. 12:1993;3467-3473.
60. Nimnual AS, Yatsula BA, Bar-Sagi D. Coupling of Ras and Rac guanosine triphosphatases through the Ras exchanger Sos. of special interest Science. 279:1998;560-563 This study provides interesting new data on Sos. The Dbl homology (DH) and PH domains of Sos activate Rac in a Ras-dependent manner. These results couple Rac and Ras signaling pathways in cellular proliferation and actin polymerisation.
61. Sakisaka T, Itoh T, Miura K, Takenawa T. Phosphatidylinositol 4,5-bisphosphate phosphatase regulates the rearrangement of actin filaments. Mol Cell Biol. 17:1997;3841-3849.
62. She HY, Rockow S, Tang J, Nishimura R, Skolnik EY, Chen M, Margolis B, Li W. Wiskott-Aldrich Syndrome protein is associated with the adapter protein Grb2 and the epidermal growth factor receptor in living cells. Mol Biol Cell. 8:1997;1709-1721.
63. Pandey A, Duan H, Dixit VM. Characterization of a novel Src-like adapter protein that associates with the Eck receptor tyrosine kinase. J Biol Chem. 270:1995;19201-19204.
64. Pandey A, Lazar DF, Saltiel AR, Dixit VM. Activation of the Eck receptor protein tyrosine kinase stimulates phosphatidylinositol 3-kinase activity. J Biol Chem. 269:1994;30154-30157.
65. Wennström S, Siegbahn A, Yokote K, Arvidsson A-K, Heldin C-H, Mori S, Claesson-Welsh L. Membrane ruffling and chemotaxis transduced by the PDGF β-receptor require the binding site for phosphatidylinositol 3′ kinase. Oncogene. 9:1994;651-660.
66. Kundra V, Escobedo JA, Kazlauskas A, Kim HK, Rhee SG, Williams LT, Zetter BR. Regulation of chemotaxis by the platelet-derived growth factor receptor-β Nature. 367:1994;474-476.
67. Nobes CD, Hawkins P, Stephens L, Hall A. Activation of the small GTP-binding proteins rho and rac by growth factor receptors. J Cell Sci. 108:1995;225-233.
68. Hawkins PT, Eguinoa A, Qui R-G, Stokoe D, Cooke FT, Walters R, Wennström S, Claesson-Welsch L, Evans T, Symons M, Stephens L. PDGF stimulates an increase in GTP-Rac via activation of phosphoinositide 3-kinase. Curr Biol. 5:1995;393-403.
69. Ponting CP. SAM: a novel motif in yeast sterile and Drosophila polyhomeotic proteins. Protein Sci. 4:1995;1928-1930.
70. Schultz J, Ponting CP, Holfmann K, Bork P. SAM as a protein interaction domain involved in developmental regulation. of special interest Protein Sci. 6:1997;249-253 Careful alignment of sequences has revealed the presence of SAM domains in a variety of developmentally important proteins, including the family of Eph receptors.
71. Songyang Z, Fanning AS, Fu C, Xu J, Marfatia SM, Chishi AH, Crompton A, Chan AC, Anderson JM, Cantley LC. Recognition of unique carboxyl-terminal motifs by distinct PDZ domains. Science. 275:1997;73-77.
72. Sheng M. PDZs and receptor/channel clustering: rounding up the latest suspects. Neuron. 17:1996;575-578.
73. Tsunoda S, Sierralta J, Sun Y, Bodner R, Suzuki E, Becker A, Socolich M, Zuker CS. A multivalent PDZ-domain protein assembles signaling complexes in a G-protein-coupled cascade. Nature. 388:1997;243-249.
74. Böhme B, VandenBos T, Ceretti DP, Park LS, Holtrich U, Rübsamen-Waigmann H, Strebhardt K. Cell - cell adhesion mediated by binding of membrane-anchored ligand LERK-2 to the EPH-related receptor human embryonal kinase 2 promotes tyrosine kinase activity. J Biol Chem. 271:1996;24747-24752.
75. Holash JA, Soans C, Chong LD, Shao H, Dixit VM, Pasquale EB. Reciprocal expression of the Eph receptor Cek5 and its ligand(s) in the early retina. Dev Biol. 182:1997;256-269.
76. Chiarugi PC, Cirri P, Marra F, Raugei G, Fiaschi T, Camici G, Manao G, Romanelli RG, Ramponi G. The src and signal tranducers and activators of transcription pathways as signal targets for low molecular weight phosphotyrosine-protein phosphatase in platelet-derived growth factor signaling. J Biol Chem. 273:1998;6776-6785.
77. Winning RS, Scales JB, Sargent TD. Disruption of cell adhesion in Xenopus embryos by Pagliaccio, an Eph-class receptor tyrosine kinase. Dev Biol. 179:1996;309-319.
78. Zisch AH, Stallcup WB, Chong LD, Dahlin-Huppe K, Voshol J, Schachner M, Pasquale EB. Tyrosine phosphorylation of L1 family adhesion molecules: implication of the Eph kinase Cek5. J Neurosci Res. 47:1997;655-665.
79. Burden-Gulley SM, Pendergast M, Lemmon V. The role of cell adhesion molecule L1 in axonal extension, growth cone motility, a signal transduction. Cell Tissue Res. 290:1997;415-422.
80. Cohen NR, Taylor JSH, Scott LB, Guillery RW, Soriano P, Furley AJW. Erros in corticospinal axon guidance in mice lacking the neural cell adhesion molecule L1. Curr Biol. 8:1997;26-33.
81. Massague J, Pandiella A. Membrane-anchored growth factors. Annu Rev Biochem. 62:1993;515-541.
82. Gale NW, Flenniken A, Compton DC, Jenkins N, Copeland NG, Gilbert DJ, Davis S, Wilkinson D, Yancopoulos GD. Elk-L3, a novel transmembrane ligand for the Eph family of receptor tyrosine kinases. Oncogene. 13:1996;1343-1352.
83. Brückner K, Pasquale EB, Klein R. Tyrosine phosphorylation of transmembrane ligands for Eph receptors. of outstanding interest Science. 275:1997;1640-1643 This paper describes two possible mechanisms for ephrin-B ligand phosphorylation. Together with [87] it shows that EphB2 receptor contact triggers ephrin-B phosphorylation. In additon, it demonstrates ephrin-B phosphorylation in a crosstalk with an activated RTK.
84. Henkemeyer M, Orioli D, Henderson JT, Saxton TM, Roder J, Pawson T, Klein R. Nuk controls pathfinding of commissural axons in the mammalian central nervous system. of outstanding interest Cell. 86:1996;35-46 This knockout study shows that EphB2 is required for correct formation of the anterior commissure in mice. Anterior commissure formation is nearly normal in mice expressing a kinase-dead EphB2 receptor, providing the first genetic evidence for an active signaling role of ephrin-B ligands.
85. Brambilla R, Brückner K, Orioli D, Bergemann AD, Flanagan JG, Klein R. Similarities and differences in the way transmembrane-type ligands interact with the elk subclass of eph receptors. Mol Cell Neurosci. 8:1996;199-209.
86. Orioli D, Henkemeyer M, Lemke G, Klein R, Pawson T. Sek4 and Nuk receptors cooperate in guidance of commissural axons and in palate formation. EMBO J. 15:1996;6035-6049.
87. Holland SJ, Gale NW, Mbamalu G, Yancopoulos GD, Henkemeyer M, Pawson T. Bidirectional signaling through the EPH-family receptor Nuk and its transmembrane ligands. of outstanding interest Nature. 1996;722-725 This paper describes Eph receptor-induced tyrosine phosphorylation of ephrin-B ligands in a neuronal cell line and presents the first biochemical evidence for bidirectional signaling in the Eph-ephrin systems.
88. Wu C, Butz S, Ying Y-s, Anderson RGW. Tyrosine kinase receptors concentrated in caveoale-like domains from neuronal plasma membrane. of special interest J Biol Chem. 272:1997;3554-3559 This study identified a number of RTKs, including an Eph receptor and an ephrin, in caveolae-like domains suggesting roles in signal transduction.
89. Simons K, Ikonen E. Functional rafts in cell membranes. Nature. 387:1997;569-572.
90. Harder T, Simons K. Caveolae, DIGs, and the dynamics of sphingolipid - cholesterol microdomains. Curr Opin Cell Biol. 9:1997;534-542.
91. Brown D. The tyrosine kinase connection: how GPI-anchored proteins activate T cells. Curr Opin Immunol. 5:1993;349-354.