1kgy

Structural highlights

Function

[EPHB2_MOUSE] Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Functions in axon guidance during development. Involved in the guidance of commissural axons, that form a major interhemispheric connection between the 2 temporal lobes of the cerebral cortex. Also involved in guidance of contralateral inner ear efferent growth cones at the midline and of retinal ganglion cell axons to the optic disk. Beside axon guidance, also regulates dendritic spines development and maturation and stimulates the formation of excitatory synapses. Upon activation by EFNB1, abolishes the ARHGEF15-mediated negative regulation on excitatory synapse formation. Controls other aspects of development including angiogenesis, palate development and in inner ear development through regulation of endolymph production. Forward and reverse signaling through the EFNB2/EPHB2 complex regulate movement and adhesion of cells that tubularize the urethra and septate the cloaca. May function as a tumor suppressor.^{[1] [2] [3] [4] [5] [6] [7]} [EFNB2_MOUSE] Cell surface transmembrane ligand for Eph receptors, a family of receptor tyrosine kinases which are crucial for migration, repulsion and adhesion during neuronal, vascular and epithelial development. Binds promiscuously Eph receptors residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Binds to receptor tyrosine kinase including EPHA4, EPHA3 and EPHB4. Together with EPHB4 plays a central role in heart morphogenesis and angiogenesis through regulation of cell adhesion and cell migration. EPHB4-mediated forward signaling controls cellular repulsion and segregation from EFNB2-expressing cells. May play a role in constraining the orientation of longitudinally projecting axons.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

• Ephrin
• Ephrin receptor 3D structures

References

1. ↑ 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. Cell. 1996 Jul 12;86(1):35-46. PMID:8689685
2. ↑ 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. 1996 Nov 15;15(22):6035-49. PMID:8947026
3. ↑ Adams RH, Wilkinson GA, Weiss C, Diella F, Gale NW, Deutsch U, Risau W, Klein R. Roles of ephrinB ligands and EphB receptors in cardiovascular development: demarcation of arterial/venous domains, vascular morphogenesis, and sprouting angiogenesis. Genes Dev. 1999 Feb 1;13(3):295-306. PMID:9990854
4. ↑ Cowan CA, Yokoyama N, Bianchi LM, Henkemeyer M, Fritzsch B. EphB2 guides axons at the midline and is necessary for normal vestibular function. Neuron. 2000 May;26(2):417-30. PMID:10839360
5. ↑ Henkemeyer M, Itkis OS, Ngo M, Hickmott PW, Ethell IM. Multiple EphB receptor tyrosine kinases shape dendritic spines in the hippocampus. J Cell Biol. 2003 Dec 22;163(6):1313-26. PMID:14691139 doi:http://dx.doi.org/10.1083/jcb.200306033
6. ↑ Dravis C, Yokoyama N, Chumley MJ, Cowan CA, Silvany RE, Shay J, Baker LA, Henkemeyer M. Bidirectional signaling mediated by ephrin-B2 and EphB2 controls urorectal development. Dev Biol. 2004 Jul 15;271(2):272-90. PMID:15223334 doi:http://dx.doi.org/10.1016/j.ydbio.2004.03.027
7. ↑ Margolis SS, Salogiannis J, Lipton DM, Mandel-Brehm C, Wills ZP, Mardinly AR, Hu L, Greer PL, Bikoff JB, Ho HY, Soskis MJ, Sahin M, Greenberg ME. EphB-mediated degradation of the RhoA GEF Ephexin5 relieves a developmental brake on excitatory synapse formation. Cell. 2010 Oct 29;143(3):442-55. doi: 10.1016/j.cell.2010.09.038. PMID:21029865 doi:http://dx.doi.org/10.1016/j.cell.2010.09.038
8. ↑ Himanen JP, Rajashankar KR, Lackmann M, Cowan CA, Henkemeyer M, Nikolov DB. Crystal structure of an Eph receptor-ephrin complex. Nature. 2001 Dec 20-27;414(6866):933-8. PMID:11780069 doi:10.1038/414933a