Vav is associated with signal transducing molecules gp130, Grb2 and Erk2, and is tyrosine phosphorylated in response to interleukin-6.
Vav is a hematopoietic cell-specific proto-oncogene. We show that interleukin-6 (IL-6) induces transient tyrosine phosphorylation of Vav in a human myeloma cell line, U266. A membrane-distal part of the cytoplasmic region of gp130 is critical for association between Vav and gp130, and the IL-6-induced tyrosine phosphorylation of Vav. Mitogen-activated protein kinase (MAPK) (p42MAPK or extracellular signal-regulated kinase 2 (Erk2)) is coprecipitated with Vav. MAPK activity in the anti-Vav immunoprecipitates is upregulated by IL-6 stimulation. Furthermore Vav is associated with Grb2 which is known as an adapter protein leading to Ras activation. The results imply that Vav may link gp130 activation to downstream MAPK activation in hematopoietic cells.
Lee
I S
IS
Institute for Molecular and Cellular Biology, Osaka University, Suita, Japan.
Liu
Y
Y
Narazaki
M
M
Hibi
M
M
Kishimoto
T
T
Taga
T
T
D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD / Q000378:metabolism*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002462:Cell Membrane / Q000378:metabolism; D050822:Cytokine Receptor gp130; D051380:GRB2 Adaptor Protein; D006801:Humans; D015850:Interleukin-6 / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1; D010766:Phosphorylation; D011233:Precipitin Tests; D011506:Proteins / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051567:Proto-Oncogene Proteins c-vav; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; D018797:Cell Cycle Proteins; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; C494199:IL6ST protein, human; D015850:Interleukin-6; C000715470:MAS1 protein, human; D008562:Membrane Glycoproteins; D011506:Proteins; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D051567:Proto-Oncogene Proteins c-vav; D011994:Recombinant Proteins; C496618:VAV1 protein, human; D050822:Cytokine Receptor gp130; D014443:Tyrosine; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1