Protein kinase C-dependent release of a functional whole extracellular domain of the mast cell growth factor (MGF) receptor by MGF-dependent human myeloid cells.
The mast cell growth factor (MGF) affects migration, proliferation and differentiation of erythroid and myeloid progenitor cells by binding to a transmembrane receptor tyrosine kinase encoded by the c-Kit proto-oncogene. By using MGF-dependent human myeloid cell lines (M-07e and TF-1), here we show that a Kit-related 100 kDa protein is associated with the cell but it undergoes release into the medium upon treatment with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), an activator of protein kinase C. Immunological analysis with a series of antibodies to Kit indicated that the released protein (p100Kit) contains the whole glycosylated extracellular portion of the transmembrane Kit protein (p145Kit). The secreted protein retained the ability to specifically bind MGF. Moreover, p100Kit was able to block the mitogenic effect of MGF on cultured M-07e cells, suggesting that the soluble protein may function as a physiological antagonist of MGF.
Brizzi
M F
MF
Dipartimento di Scienze Biomediche e Oncologia Umana, Universitá di Torino, Italy.
Blechman
J M
JM
Cavalloni
G
G
Givol
D
D
Yarden
Y
Y
Pegoraro
L
L
D000818:Animals; D001854:Bone Marrow Cells; D016466:CHO Cells; D002478:Cells, Cultured; D006224:Cricetinae; D016298:Hematopoietic Cell Growth Factors / Q000037:antagonists & inhibitors / Q000502:physiology*; D006801:Humans; D010766:Phosphorylation; D011493:Protein Kinase C / Q000502:physiology*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000032:analysis*; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis*; D016184:Receptors, Colony-Stimulating Factor / Q000032:analysis*; D019089:Stem Cell Factor; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D016298:Hematopoietic Cell Growth Factors; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D016184:Receptors, Colony-Stimulating Factor; D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate