Insulin-dependent tyrosine phosphorylation of the vav protooncogene product in cells of hematopoietic origin.

The Journal of Biological Chemistry
S UddinL C Platanias

Abstract

Insulin activates the ras signaling pathway and promotes hematopoietic cell proliferation. One possible mediator in such signaling is the vav proto-oncogene product (p95vav), which is specifically expressed in cells of hematopoietic origin and contains domains typical of guanine nucleotide exchange factors as well as Src homology 2 and Src homology 3 domains. We studied the tyrosine phosphorylation of p95vav in hematopoietic cells expressing insulin receptors. Immunoblotting experiments with an antiphosphotyrosine monoclonal antibody disclosed that insulin induces rapid and transient tyrosine phosphorylation of p95vav in the human U-266 myeloma cell line. These findings were confirmed by immunoprecipitation experiments performed with 32P-labeled cells and phosphoamino acid analysis of the bands corresponding to p95vav. Similarly, insulin-dependent tyrosine phosphorylation of p95vav was observed in the human IM-9 and mouse J558L hematopoietic cell lines. Furthermore, insulin treatment of cells led to the association of the Src homology 2 domain of p95vav with the activated beta-subunit of the insulin receptor in vitro. Altogether, these data suggest that p95vav is a substrate for the insulin receptor tyrosine kinase and may be i...Continue Reading

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Citations

Mar 29, 2000·Biochemical and Biophysical Research Communications·S UddinL C Platanias
Dec 1, 1996·Cellular Signalling·F Romero, S Fischer
Feb 12, 2000·Molecular and Cellular Biology·X R Bustelo
Apr 23, 1999·Journal of Basic and Clinical Physiology and Pharmacology·M A Rizzo, G Romero
May 1, 1996·Stem Cells·N Bonnefoy-BérardA Altman
Mar 31, 2004·Experimental Hematology·Elena AlmarzaJuan Antonio Bueren
Jan 18, 2005·Cancer Cell·Martin E Fernandez-ZapicoDaniel D Billadeau
Jan 5, 1999·The Journal of Biological Chemistry·E N FishL C Platanias
Jan 5, 1996·The Journal of Biological Chemistry·L C PlataniasM F White
Aug 4, 1995·The Journal of Biological Chemistry·A YetterL C Platanias
Feb 13, 2001·British Journal of Haematology·I M GrumbachL C Platanias
May 1, 1997·Experimental Cell Research·D J Denkinger, R S Kawahara
Jun 9, 1997·Biochemical and Biophysical Research Communications·S UddinL C Platanias

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