Steel factor stimulates the tyrosine phosphorylation of the proto-oncogene product, p95vav, in human hemopoietic cells.
Steel factor (SF) (also called stem cell factor, mast cell growth factor, or c-kit ligand) is a recently cloned hemopoietic growth factor that is produced by bone marrow stromal cells, fibroblasts, and hepatocytes. In both mouse and man it acts synergistically with several colony stimulating factors, including interleukin-3 (IL-3) and granulocyte macrophage-colony stimulating factor (GM-CSF), to induce the proliferation and differentiation of primitive hemopoietic precursor cells. In order to study its mechanism of action and to explore the molecular basis for its synergistic activity we have examined the proteins that become tyrosine phosphorylated in response to SF, IL-3, and GM-CSF. We report herein that SF, but not IL-3 or GM-CSF, dramatically stimulates the tyrosine phosphorylation of the product of the recently discovered proto-oncogene, vav, in two SF-responsive human cell lines, M07E and TF-1. Although phosphorylation is very rapid, reaching maximal levels within 2 min at 37 degrees C, co-immunoprecipitation studies suggest that c-kit may either not associate directly with p95vav or bind to it with very low affinity. Nonetheless, our data suggest that c-kit may utilize p95vav to mediate downstream signaling in hemopoietic cells.
Alai
M
M
Terry Fox Laboratory, British Columbia Cancer Research Centre, Vancouver, Canada.
Mui
A L
AL
Cutler
R L
RL
Bustelo
X R
XR
Barbacid
M
M
Krystal
G
G
D000818:Animals; D000911:Antibodies, Monoclonal; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology*; D006410:Hematopoiesis / Q000187:drug effects; D016298:Hematopoietic Cell Growth Factors / Q000276:immunology / Q000494:pharmacology*; D006801:Humans; D007947:Leukemia, Megakaryoblastic, Acute; D015470:Leukemia, Myeloid, Acute; D015513:Oncogene Proteins / Q000378:metabolism*; D010750:Phosphoproteins / Q000302:isolation & purification; D010766:Phosphorylation; D019000:Phosphotyrosine; D000090063:Proto-Oncogene Mas; D051567:Proto-Oncogene Proteins c-vav; D011994:Recombinant Proteins / Q000494:pharmacology; D019089:Stem Cell Factor; D014162:Transfection; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000032:analysis
D000911:Antibodies, Monoclonal; D016207:Cytokines; D016298:Hematopoietic Cell Growth Factors; C000715470:MAS1 protein, human; D015513:Oncogene Proteins; D010750:Phosphoproteins; D000090063:Proto-Oncogene Mas; D051567:Proto-Oncogene Proteins c-vav; D011994:Recombinant Proteins; D019089:Stem Cell Factor; C496618:VAV1 protein, human; D019000:Phosphotyrosine; D014443:Tyrosine