Type XIII RTKs: Ephrin receptor family: Introduction

Ephrin receptors (EphRs) are receptor tyrosine kinases. The main function of the EphRs is mediation of contact-dependent cell-cell communication, via interaction with membrane-bound ephrin ligands. EphR-ephrin complexes generate bidirectional signals with effects on both the receptor- and ligand-expressing cells. "Forward" signaling involves prototypical activation of the receptors' RTK domain upon ligand interaction, but also by receptor-receptor cis interactions (or receptor clustering) [2,9]. EphRs regulate effector proteins including Rho and Ras GTPases and Akt/mTORC1. "Reverse" signalling occurs in the ephrin-expressing cells, a function that appears to be mediated by ephrin-B phosphorylation by Src family kinases. The ephrin signalling pathway is active in many developmental processes and in adult tissue homeostasis [1,3-5,7]. Aberrant ephrin pathway function has been implicated in cancer, and in particular its role in tumour neoangiogensis [8], highlights elements of this pathway as oncology drug targets [1,6].

References

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1. Genander M, Frisén J. (2010) Ephrins and Eph receptors in stem cells and cancer. Curr. Opin. Cell Biol., 22 (5): 611-6. [PMID:20810264]

2. Himanen JP, Yermekbayeva L, Janes PW, Walker JR, Xu K, Atapattu L, Rajashankar KR, Mensinga A, Lackmann M, Nikolov DB et al.. (2010) Architecture of Eph receptor clusters. Proc. Natl. Acad. Sci. U.S.A., 107 (24): 10860-5. [PMID:20505120]

3. Kania A, Klein R. (2016) Mechanisms of ephrin-Eph signalling in development, physiology and disease. Nat. Rev. Mol. Cell Biol., 17 (4): 240-56. [PMID:26790531]

4. Pasquale EB. (2005) Eph receptor signalling casts a wide net on cell behaviour. Nat. Rev. Mol. Cell Biol., 6 (6): 462-75. [PMID:15928710]

5. Pasquale EB. (2008) Eph-ephrin bidirectional signaling in physiology and disease. Cell, 133 (1): 38-52. [PMID:18394988]

6. Pasquale EB. (2010) Eph receptors and ephrins in cancer: bidirectional signalling and beyond. Nat. Rev. Cancer, 10 (3): 165-80. [PMID:20179713]

7. Peuckert C, Aresh B, Holenya P, Adams D, Sreedharan S, Porthin A, Andersson L, Pettersson H, Wölfl S, Klein R et al.. (2016) Multimodal Eph/Ephrin signaling controls several phases of urogenital development. Kidney Int., 90 (2): 373-388. [PMID:27344203]

8. Rudno-Rudzińska J, Kielan W, Frejlich E, Kotulski K, Hap W, Kurnol K, Dzierżek P, Zawadzki M, Hałoń A. (2017) A review on Eph/ephrin, angiogenesis and lymphangiogenesis in gastric, colorectal and pancreatic cancers. Chin. J. Cancer Res., 29 (4): 303-312. [PMID:28947862]

9. Seiradake E, Harlos K, Sutton G, Aricescu AR, Jones EY. (2010) An extracellular steric seeding mechanism for Eph-ephrin signaling platform assembly. Nat. Struct. Mol. Biol., 17 (4): 398-402. [PMID:20228801]

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To cite this family introduction, please use the following:

Type XIII RTKs: Ephrin receptor family, introduction. Last modified on 26/02/2018. Accessed on 23/11/2020. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyIntroductionForward?familyId=327.