Thrombopoietin induces activation of the phosphatidylinositol-3′ kinase pathway and formation of a complex containing p85PI3K and the protooncoprotein p120CBL

Autor: Ravi Salgia, Martin Sattler, K. V S Prasad, M. Durstin, James D. Griffin
Rok vydání: 1997
Předmět:
Zdroj: Journal of Cellular Physiology. 171:28-33
ISSN: 1097-4652
0021-9541
DOI: 10.1002/(sici)1097-4652(199704)171:1<28::aid-jcp4>3.0.co;2-j
Popis: Thrombopoietin (TPO) promotes megakaryocyte growth and development. Its receptor, c-MPL, is restricted to cells of megakaryocytic lineage and stem cells. We have previously shown that activation of c-MPL by thrombopoietin rapidly activates at least two cytoplasmic tyrosine kinases, JAK2 and TYK2, after ligand binding. Phosphatidylinositol-3' kinase (PI3K) has been shown to play an important role in downstream signaling for many receptors. Thrombopoietin was found to also rapidly activate phosphatidylinositol-3' kinase, and the phosphatidylinositol-3' kinase inhibitor wortmannin decreased proliferation of thrombopoietin-stimulated cells, implying that phosphatidylinositol-3' kinase may have a regulatory role in thrombopoietin signaling. In immunoprecipitation studies, the regulatory subunit of phosphatidylinositol-3' kinase, p85PI3K, associated with several tyrosine phosphoproteins, and the major phosphoprotein was a 120 kDa protein identified as p120CBL. The phosphatidylinositol-3' kinase-enzyme activity in p120CBL immunoprecipitates was elevated in thrombopoietin-stimulated cells as compared to immunoprecipitates from unstimulated cells. p120CBL may be involved in signaling pathways activated by c-MPL which involve phosphatidylinositol-3' kinase.
Databáze: OpenAIRE
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