Ephrin receptor

Ephrin receptors ( Eph engl. receptor, Eph ) are receptors that are activated by binding of ephrins. They form the largest known subfamily of receptor tyrosine kinases ( RTK). Both ephrin receptors and their ligands are membrane proteins that require the activation of a direct contact between cells. An Ephrin- dependent signal is examined in relation to embryogenesis, the polarization direction of the growth of axons, cell migration and segmentation. Further, an influence in various processes in the adult, for example, in the long-term potentiation of angiogenesis, differentiation of stem cells and cancer has been determined.

Ephrinrezeptor subclasses

Ephrin receptors are divided into two subclasses, EphA and EphB (Gene Health Alliance and EphB ) based on their binding affinity for glycosylphosphatidylinositol -anchored ephrin - A ligands or transmembrane ephrin - B ligands. Among the sixteen discovered in animals ephrin people have only nine EphA ( EphA1 -8 and EphA10 ) and five EphB ( EphB1 -4 and EphB6 ). Ephrins bind specifically within their subclass. Exceptions are the binding of Ephrin- B3 Eph -A4 and the binding of ephrin -A5 on Eph B2. The bonds within the subclass A is usually more specific than in the subclass B, which is attributed to the fact that the binding in subclass A for a key - lock principle with less conformational changes takes place as in the subclass B with an induced fit.

The following 16 ephrin receptors have been found in animals: EphA1, EPHA2, EphA3, EPHA4, EPHA5, EPHA6, EphA7, EPHA8, EPHA9, EPHA10 * EphB1, EPHB2, EphB3, EphB4, EPHB5, EphB6

Activation

The extracellular domain of the Ephrinrezeptors consists of a conserved globular Ephrinbindungsdomäne, a cysteine ​​-rich region and two fibronectin type - 3 domains. The cytoplasmic fraction consists of a membranangrenzenden kinase domain with two tyrosines, a sterile alpha motif (SAM ) and a PDZ domain - binding motif. After binding of a ligand Tyrosine and Serine are phosphorylated at Ephrinrezeptor whereby the Tyrosinkinasefunktion is activated.

In contrast to most other receptor ephrin receptors have the unique ability to stimulate signal transduction in both cells involved. This is probably a reason for the different effects caused by activation of ephrin receptors, for example, on the survival of growth cones, or the separation of Ephrin and Ephrinrezeptor - expressing cells.

History

Ephrin receptors were first identified in 1987 in search of RTK with a reference to cancer in the cell line erythropoietin -producing hepatocellular carcinoma.

After it was shown that almost all ephrin receptors occur in different stages of development as well as spatially limited, ephrin receptors were known as the main receptors of the cell control during the development of invertebrates and vertebrates.