STEM-CELL FACTOR INDUCES PHOSPHORYLATION OF A 200 KDA PROTEIN WHICH ASSOCIATES WITH C-KIT

Stem cell factor (SCF) promotes limited proliferation and differentiat ion of hematopoietic progenitor cells and is potently synergistic in c ombination with growth factors such as granulocyte-macrophage colony s timulating factor (GM-CSF), interleukin 3 (IL-3) or erythropoietin (Ep o). We have examined tyrosine phosphorylation induced by SCF in the me gakaryoblastic 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 l abeling of Mo7e cells suggested that p200 had an extracellular domain and could be induced to associate with c-kit after stimulation with SC F. The rapid phosphorylation of p200 and its immediate association wit h c-kit suggest that p200 is potentially a component of the SCF signal transduction pathway.