ACTIVATION OF THE ECK RECEPTOR PROTEIN-TYROSINE KINASE STIMULATES PHOSPHATIDYLINOSITOL 3-KINASE ACTIVITY

The Eph/Eck subfamily of receptor protein tyrosine kinases is currentl y the largest subfamily of receptor protein tyrosine kinases with a do zen members (Van der Geer, P., Hunter, T., and Lindberg, R. A. (1994) Annu. Rev. Cell Biol. 10, 251-337). Using the cytoplasmic domain of Ec k as bait in a yeast two-hybrid screen of mouse embryonic and T cell c DNA libraries, it was discovered that the p85 subunit of phosphatidyli nositol 3-kinase bound Eck. Further, using glutathione S-transferase f usion proteins, it was found that the C-terminal src homology 2 domain of the p85 subunit specifically interacted with Eck. Additionally, Ec k coimmunoprecipitated with p85 in ligand activated cells confirming t heir interaction in vivo. In keeping with the above observations, acti vation of Eck by its ligand, B61, increased phosphatidylinositol 3-kin ase activity. This is the first description of a signal transduction p athway initiated by any member of the Eph/Eck family.