Protein kinase C dependent induction of pp125FAK in monocytes by colony stimulating factor-GM: evidence for a synergistic effect by the cytokine and 1,25 dihydroxyvitamin D3.
The differentiation of monocytes into osteoclasts has been recently achieved in vitro in a suitable milieu containing morphogens that includes 1,25 dihydroxyvitamin D3, colony stimulating factors, interleukins and the presence of cells of osteoblastic lineage. However, the precise role of these factors in the osteoclastic differentiation process has not yet been examined. Since our previous studies have shown that osteoclasts express a much higher level of focal adhesion kinase (pp125FAK) than cells of macrophage/monocytic lineage, the present study was carried out to ascertain which morphogens are involved in increasing the expression of the kinase during the differentiation of monocytes to osteoclasts. We demonstrate that a marked increase in the expression of pp125FAK occurs only after prolonged exposure to hCSF-GM and combination of hCSF-GM and 1,25 (OH)2 D3. The hCSF-GM was found to be a more potent stimulator of pp125FAK induction than 1,25 (OH)2 D3; interestingly, the presence of both hCSF-GM and 1,25 (OH)2 D3 showed co-operative effect. Furthermore, the presence of a protein kinase C inhibitor, bisindolylmaleimide (GF 109203X), blocked hCSF-GM-mediated induction of focal adhesion kinase, implicating an important role for protein kinase C in the induction of pp125FAK.
Kanan
R M
RM
Department of Clinical Biochemistry, Medical School, University of Newcastle, Newcastle upon Tyne, UK.
Rathod
H
H
Datta
H K
HK
D002117:Calcitriol / Q000494:pharmacology*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004357:Drug Synergism; D004790:Enzyme Induction / Q000187:drug effects; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis*; D011972:Receptor, Insulin / Q000378:metabolism*
D015815:Cell Adhesion Molecules; D007211:Indoles; D008301:Maleimides; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; D011493:Protein Kinase C; D002117:Calcitriol; C070515:bisindolylmaleimide I