Characterization of a novel Src-like adapter protein that associates with the Eck receptor tyrosine kinase.
The Eph family of receptor protein tyrosine kinases (RPTKs) is the largest family of RPTKs. The signal transduction pathways initiated by this family have only recently begun to be explored. Using a yeast two-hybrid screen to identify molecules that interact with the cytoplasmic domain of Eck, it was previously shown that activated Eck RPTK bound to and stimulated phosphatidylinositol 3-kinase (Pandey, A., Lazar, D.F., Saltiel, A. R., and Dixit, V.M. (1994) J. Biol. Chem. 269, 30154-30157). Also isolated from this same screen was a novel protein containing SH3 and SH2 adapter modules that had striking homology to those found in the Src family of non-receptor tyrosine kinases. However, unlike other Src family members, it lacked a catalytic tyrosine kinase domain. Hence, this protein was designated SLAP for Src-like adapter protein. Using glutathione S-transferase fusion Proteins, it was demonstrated that SLAP bound to activated Eck receptor tyrosine kinase. Therefore, SLAP is a novel candidate downstream signaling intermediate and the first member of the Src family that resembles an adapter molecule.
Pandey
A
A
Department of Pathology University of Michigan Medical School, Ann Arbor 48109-0602, USA.
Duan
H
H
Dixit
V M
VM
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D018076:DNA, Complementary; D036382:Ephrin-A1; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D036104:Receptor, EphA2; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D048868:Adaptor Proteins, Signal Transducing; D018076:DNA, Complementary; D036382:Ephrin-A1; D008565:Membrane Proteins; D011506:Proteins; D011993:Recombinant Fusion Proteins; C490636:Sla protein, rat; D005982:Glutathione Transferase; D020794:Receptor Protein-Tyrosine Kinases; D036104:Receptor, EphA2; D016392:Proto-Oncogene Proteins pp60(c-src)