Activation of the Eck receptor protein tyrosine kinase stimulates phosphatidylinositol 3-kinase activity.
The Eph/Eck subfamily of receptor protein tyrosine kinases is currently the largest subfamily of receptor protein tyrosine kinases with a dozen members (Van der Geer, P., Hunter, T., and Lindberg, R. A. (1994) Annu. Rev. Cell Biol. 10, 251-337). Using the cytoplasmic domain of Eck as bait in a yeast two-hybrid screen of mouse embryonic and T-cell cDNA libraries, it was discovered that the p85 subunit of phosphatidylinositol 3-kinase bound Eck. Further, using glutathione S-transferase fusion proteins, it was found that the C-terminal src homology 2 domain of the p85 subunit specifically interacted with Eck. Additionally, Eck coimmunoprecipitated with p85 in ligand activated cells confirming their interaction in vivo. In keeping with the above observations, activation of Eck by its ligand, B61, increased phosphatidylinositol 3-kinase activity. This is the first description of a signal transduction pathway initiated by any member of the Eph/Eck family.
Pandey
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A
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0602.
Lazar
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DF
Saltiel
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AR
Dixit
V M
VM
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002478:Cells, Cultured; D003001:Cloning, Molecular; D017931:DNA Primers; D018076:DNA, Complementary / Q000378:metabolism; D004622:Embryo, Mammalian; D004789:Enzyme Activation; D015870:Gene Expression; D015723:Gene Library; D005982:Glutathione Transferase / Q000378:metabolism; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000201:enzymology; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats; D036104:Receptor, EphA2; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D013601:T-Lymphocytes / Q000201:enzymology; D014158:Transcription, Genetic
D017931:DNA Primers; D018076:DNA, Complementary; D005982:Glutathione Transferase; D046911:Macromolecular Substances; D008565:Membrane Proteins; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D011505:Protein-Tyrosine Kinases; D036104:Receptor, EphA2; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins