cd05033

Catalytic domain of Ephrin Receptor Protein Tyrosine Kinases

CDD entry
Member databaseCDD
CDD typedomain
Short namePTKc_EphR
SetPKc_like

Description

PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EphRs comprise the largest subfamily of receptor PTKs (RTKs). They can be classified into two classes (EphA and EphB), according to their extracellular sequences, which largely correspond to binding preferences for either GPI-anchored ephrin-A ligands or transmembrane ephrin-B ligands. Vertebrates have ten EphA and six EphB receptors, which display promiscuous ligand interactions within each class. EphRs contain an ephrin binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. This allows ephrin/EphR dimers to form, leading to the activation of the intracellular tyr kinase domain. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). The main effect of ephrin/EphR interaction is cell-cell repulsion or adhesion. Ephrin/EphR signaling is important in neural development and plasticity, cell morphogenesis and proliferation, cell-fate determination, embryonic development, tissue patterning, and angiogenesis.The EphR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.
[12, 2, 7, 16, 13, 5, 1, 9, 4, 10, 15, 8, 14, 6, 3, 11]

References

1.Eph receptor and ephrin ligand-mediated interactions during angiogenesis and tumor progression. Heroult M, Schaffner F, Augustin HG. Exp Cell Res 312, 642-50, (2006). PMID: 16330025

2.Role of the ephrin and Eph receptor tyrosine kinase families in angiogenesis and development of the cardiovascular system. Zhang J, Hughes S. J Pathol 208, 453-61, (2006). PMID: 16470907

3.Protein tyrosine kinase structure and function. Hubbard SR, Till JH. Annu Rev Biochem 69, 373-98, (2000). PMID: 10966463

4."Eph receptor signalling; dimerisation just isn't enough". Vearing CJ, Lackmann M. Growth Factors 23, 67-76, (2005). PMID: 16019428

5.Comparative integromics on Eph family. Katoh M, Katoh M. Int J Oncol 28, 1243-7, (2006). PMID: 16596241

6.EPHB receptor signaling in dendritic spine development. Irie F, Yamaguchi Y. Front Biosci 9, 1365-73, (2004). PMID: 14977552

7.Emerging roles of the Angiopoietin-Tie and the ephrin-Eph systems as regulators of cell trafficking. Pfaff D, Fiedler U, Augustin HG. J Leukoc Biol 80, 719-26, (2006). PMID: 16864601

8.Ephrin signaling in vivo: look both ways. Davy A, Soriano P. Dev Dyn 232, 1-10, (2005). PMID: 15580616

9.Eph proteins and the assembly of auditory circuits. Cramer KS. Hear Res 206, 42-51, (2005). PMID: 16080997

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

11.Structural analysis of receptor tyrosine kinases. Hubbard SR. Prog Biophys Mol Biol 71, 343-58, (1999). PMID: 10354703

12.Bidirectional ephrin/Eph signaling in synaptic functions. Aoto J, Chen L. Brain Res 1184, 72-80, (2007). PMID: 17166489

13.Roles of Eph receptors and ephrins in the normal and damaged adult CNS. Goldshmit Y, McLenachan S, Turnley A. Brain Res Rev 52, 327-45, (2006). PMID: 16774788

14.Ephrins and their receptors: binding versus biology. Blits-Huizinga CT, Nelersa CM, Malhotra A, Liebl DJ. IUBMB Life 56, 257-65, (2004). View articlePMID: 15370889

15.Eph receptors: two ways to sharpen boundaries. Sela-Donenfeld D, Wilkinson DG. Curr Biol 15, R210-2, (2005). PMID: 15797015

16.Putative dual role of ephrin-Eph receptor interactions in inflammation. Ivanov AI, Romanovsky AA. IUBMB Life 58, 389-94, (2006). PMID: 16801213

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