Proliferative but not nonproliferative responses to granulocyte colony-stimulating factor are associated with rapid activation of the p21ras/MAP kinase signalling pathway.
Granulocyte colony-stimulating factor (G-CSF) can elicit responses that include proliferation, granulocytic differentiation, and activation of cellular functions in target cells. The biochemical pathways responsible for transduction of these signals from the G-CSF receptor (G-CSFR) have not been defined. In this report, we show that, in murine (NFS-60) and human (OCI-AML 1) myeloid leukemia cell lines and in murine pro-B-lymphocytic cells, BAF/B03, transfected with the murine G-CSFR, proliferative responses to G-CSF are associated with rapid activation of p42 and p44 MAP kinases and p21ras. Truncation of the cytoplasmic portion of the murine G-CSFR at residue 646 but not at residue 739 abolished G-CSF-induced stimulation of cellular proliferation as well as activation of MAP kinase and p21ras in transfected BAF/B03 cells. G-CSF-induced granulocytic differentiation of the murine leukemic cell line 32DC13(G) occurred in the absence of detectable activation of p42 MAP kinase. Nonproliferative responses to G-CSF in the human promyelocytic cell line HL-60 and in human neutrophils were similarly associated with no MAP kinase activation. These results imply that differing cellular effects of G-CSF may be involve the recruitment of differing signal transduction pathways with the p21ras/MAP kinase pathway being limited to proliferative responses.
Bashey
A
A
Section of Cell and Molecular Biology, Chester Beatty Laboratories, Institute of Cancer Research, London, UK.
Healy
L
L
Marshall
C J
CJ
D000818:Animals; D001402:B-Lymphocytes; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000096:biosynthesis / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D004789:Enzyme Activation; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D007700:Kinetics; D007951:Leukemia, Myeloid; D015473:Leukemia, Promyelocytic, Acute; D051379:Mice; D016283:Proto-Oncogene Proteins p21(ras) / Q000096:biosynthesis / Q000378:metabolism*; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction; D014162:Transfection; D014407:Tumor Cells, Cultured
D007377:Interleukin-3; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D006160:Guanosine Triphosphate; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)