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

Authors
  • Sattler, M
  • Salgia, R
  • Durstin, M A
  • Prasad, K V
  • Griffin, J D
Type
Published Article
Journal
Journal of Cellular Physiology
Publisher
Wiley
Publication Date
Apr 01, 1997
Volume
171
Issue
1
Pages
28–33
Identifiers
PMID: 9119889
Source
Medline
License
Unknown

Abstract

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.

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