Insulin-like growth factor-1 induces rapid tyrosine phosphorylation of the vav proto-oncogene product.
The vav proto-oncogene product (p95(vav)) is specifically expressed in cells of hematopoietic origin and has one src homology 2 (SH2) domain, two SH3 domains, and motifs typical of guanine exchange factors. Insulin-like growth factor-1 (IGF-1) receptors are expressed on a variety of hematopoietic cells and, upon ligand binding, mediate signals regulating hematopoietic cell proliferation. We studied the phosphorylation status of p95(var) in the U-255 human myeloma cell line, in response to IGF-1 stimulation. Immunoblotting experiments with an antiphosphotyrosine monoclonal antibody disclosed that p95(vav) is phosphorylated on tyrosine in an IGF-1-dependent manner. The tyrosine phosphorylation of 95(vav was rapid, appearing within 5 minutes of IGF-1 treatment, amd transient, diminishing by 90 minutes. Similar results were obtained when the mouse plasmacytoma J558L cell line was studied. IGF-1-dependent tyrosine phosphorylation of p95(vav) was also seen in the 32D mouse myeloid cell line that lacks expression of insulin receptor substrate (IRS) proteins, suggesting that it is not regulated by activation of the IRS-signaling system. Taken together, these data suggest that the vav proto-oncogene is a substrate for the IGF-1 receptor tyrosine++ kinase and may be involved in the signal transduction of IGF-1 in cells of hematopoietic origin.
Uddin
S
S
Department of Medicine, Loyola University Chicago, Maywood, IL, USA.
Yetter
A
A
Katzav
S
S
Hofmann
C
C
White
M F
MF
Platanias
L C
LC
D000818:Animals; D018797:Cell Cycle Proteins; D002460:Cell Line; D006801:Humans; D055504:Insulin Receptor Substrate Proteins; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051567:Proto-Oncogene Proteins c-vav; D015398:Signal Transduction
D018797:Cell Cycle Proteins; C526292:IRS1 protein, human; C526297:IRS2 protein, human; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; C526295:Irs1 protein, mouse; C526298:Irs2 protein, mouse; C000715470:MAS1 protein, human; D010750:Phosphoproteins; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D051567:Proto-Oncogene Proteins c-vav; C496618:VAV1 protein, human; C496619:Vav1 protein, mouse; D019000:Phosphotyrosine; D007334:Insulin-Like Growth Factor I; D011505:Protein-Tyrosine Kinases