Thrombin-dependent association of phosphatidylinositol-3 kinase with p60c-src and p59fyn in human platelets.
Recent studies have shown that ligand-activated growth factor receptors as well as transforming versions of nonreceptor protein-tyrosine kinases physically associate with phosphatidylinositol-3 kinase (PI-3 kinase). Reasoning that PI-3 kinase might also play a role in the normal functions of nonreceptor kinases, we sought to determine whether association with PI-3 kinase might serve as a measure of nonreceptor protein-tyrosine kinase activation under physiological conditions. We found that p60c-src as well as p59fyn, the product of another member of the src family of proto-oncogenes, physically associated with a PI kinase activity within 5 s after exposure to thrombin. Furthermore, PI kinase reaction products generated in p60v-src, p60c-src or p59fyn containing immunoprecipitates were indistinguishable, demonstrating the identity of the associated enzyme as PI-3 kinase. These findings demonstrate a thrombin-dependent interaction between p60c-src or p59fyn and PI-3 kinase and suggest a role for nonreceptor protein-tyrosine kinases in human platelet signal transduction.
Gutkind
J S
JS
Laboratory of Cellular Development and Oncology, National Institute of Dental Research, Bethesda, Maryland 20892.
Lacal
P M
PM
Robbins
K C
KC
D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D007295:Inositol Phosphates / Q000097:blood / Q000302:isolation & purification; D007700:Kinetics; D015688:Oncogene Protein pp60(v-src) / Q000096:biosynthesis / Q000097:blood* / Q000302:isolation & purification; D019869:Phosphatidylinositol 3-Kinases; D010770:Phosphotransferases / Q000096:biosynthesis / Q000097:blood* / Q000302:isolation & purification; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000097:blood* / Q000302:isolation & purification; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000097:blood* / Q000302:isolation & purification; D013917:Thrombin / Q000494:pharmacology*
D007295:Inositol Phosphates; D011518:Proto-Oncogene Proteins; D010770:Phosphotransferases; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; D015688:Oncogene Protein pp60(v-src); D013917:Thrombin