Granulocyte colony-stimulating factor-induced activation of protein kinase-C in myeloid cells Journal Article


Authors: Deshpande, R. V.; Peterson, R. H. F.; Moore, M. A. S.
Article Title: Granulocyte colony-stimulating factor-induced activation of protein kinase-C in myeloid cells
Abstract: Granulocyte colony stimulating factor (G-CSF) regulates survival, proliferation, differentiation, and activation of myeloid cells. It binds to a high affinity receptor (G-CSF-R) expressed on myeloid cells, for which the signal transduction mechanisms other than protein tyrosine kinase (PTK) activation have not been completely identified. We explored the potential involvement of protein kinase-C (PKC) in G-CSF-R signal transduction. In this report, we provide direct evidence of PKC activation by G-CSF-R. G-CSF treatment of peripheral blood neutrophils, granulocytic cell lines (HL-60, NFS-60, KG-1), and monocytic cell lines (WEHI-3B,U-937) resulted in PKC activation. Chelerythrine chloride and HA-100, an isoquinolinesulfonamide derivative, the specific inhibitors of PKC, 1,2-Bis(2-aminophenoxy)ethane N,N,N',N'-tetra-acetic acid (BAPTA), a chelator of intracellular calcium, and 3,4,5-trimethoxybenzoic acid 8-(diethylamino)-octyl ester (TMB-8), an inhibitor of intracellular calcium release, blocked G-CSF-induced PKC activation in HL-60 cells, and reduced CD11b upregulation in neutrophils, but did not affect ligand-binding or down-modulation of G-CSF-R. Methyl 2,5- dihydroxycinnamate (MDHC), a potent inhibitor of protein tyrosine kinases (PTK), also inhibited PKC activation in response to G-CSF treatment, suggesting that PKC activation may occur downstream of PTK activation. Our results demonstrate the involvement of PKC in G-CSF-R signal transduction, and suggest a common signaling pathway in myeloid cells of granulocytic and monocytic lineages.
Keywords: signal transduction; human cell; cell proliferation; animals; mice; signaling; protein binding; enzyme activation; tumor cells, cultured; enzyme activity; cytokine; neutrophil; iodine radioisotopes; enzyme inhibitors; cell transformation; leukemia, myeloid; growth regulation; neutrophils; protein kinase c; bone marrow cell; receptor; receptor affinity; alkaloids; granulocyte colony stimulating factor; granulocyte colony-stimulating factor; granulocyte; thymidine; tritium; calcium transport; myeloid; hl-60 cells; humans; human; priority journal; article; macrophage-1 antigen; egtazic acid; colony- stimulating; benzophenanthridines; gallic acid; phenanthridines
Journal Title: Journal of Cellular Biochemistry
Volume: 66
Issue: 3
ISSN: 0730-2312
Publisher: John Wiley & Sons  
Date Published: 1997-09-01
Start Page: 286
End Page: 296
Language: English
DOI: 10.1002/(sici)1097-4644(19970901)66:3<286::aid-jcb2>3.0.co;2-l
PUBMED: 9257186
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 17 March 2017 -- Source: Scopus
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  1. Malcolm A S Moore
    549 Moore