Stem cell factor induces phosphorylation of a 200 kDa protein which associates with c-kit.
Stem cell factor (SCF) promotes limited proliferation and differentiation of hematopoietic progenitor cells and is potently synergistic in combination with growth factors such as granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin 3 (IL-3) or erythropoietin (Epo). We have examined tyrosine phosphorylation induced by SCF in the megakaryoblastic cell line Mo7e and found phosphorylation of proteins of 200, 145, 120, 58 and 55 kDa. The dominant phosphotyrosylproteins in SCF treated cells were 200 and 145 kDa. Our studies indicated that the 145 kDa protein was c-kit, the receptor for SCF. Subsequent work was directed towards further characterizing the 200 kDa protein. Surface labeling of Mo7e cells suggested that p200 had an extracellular domain and could be induced to associate with c-kit after stimulation with SCF. The rapid phosphorylation of p200 and its immediate association with c-kit suggest that p200 is potentially a component of the SCF signal transduction pathway.
Laboratory of Leukocyte Biology, Frederick Cancer Research, National Cancer Institute, MD 21702, USA.
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D
Linnekin
J R
JR
Keller
D K
DK
Ferris
S M
SM
Mou
V
V
Broudy
D L
DL
Longo
D000911:Antibodies, Monoclonal; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D007947:Leukemia, Megakaryoblastic, Acute; D008565:Membrane Proteins / Q000378:metabolism*; D008970:Molecular Weight; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D015398:Signal Transduction; D019089:Stem Cell Factor / Q000378:metabolism / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D008565:Membrane Proteins; D010750:Phosphoproteins; D019089:Stem Cell Factor; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases; D019009:Proto-Oncogene Proteins c-kit