Signalling mitogenesis in 3T3 cells: role of Ca2+-sensitive, phospholipid-dependent protein kinase.
Understanding the molecular mechanisms that control cell proliferation requires the identification of the early signals important for initiating a mitogenic response. In this context, the activation of Ca2+-sensitive, phospholipid-dependent protein kinase (protein kinase C), which is stimulated by diacylglycerols and serves as a major phorbol ester receptor, may play an important part in signalling mitogenesis. This conclusion is based on two main lines of evidence. Firstly, activation of protein kinase C in intact quiescent fibroblasts is one of the earliest events elicited by a variety of growth-promoting agents including serum, platelet-derived growth factor (PDGF), vasopressin and bombesin, as judged by the increase in the phosphorylation of a cellular protein characterized by an Mr of 80 000 and a pI of 5. Secondly, the synthetic diacylglycerol, 1-oleoyl-2-acetylglycerol, which directly competes with [3H]phorbol dibutyrate for binding to specific receptors in intact 3T3 cells and rapidly stimulates protein kinase C in these cells, is a potent mitogen for Swiss 3T3 cells, acting synergistically with other growth factors. We propose that activation of protein kinase C may be one of the early signals that mediate the mitogenic effects of a variety of growth factors and peptide hormones in quiescent fibroblastic cells.
D000818:Animals; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D002460:Cell Line; D004247:DNA / Q000096:biosynthesis*; D004075:Diglycerides / Q000494:pharmacology; D004789:Enzyme Activation; D066246:ErbB Receptors; D007328:Insulin / Q000494:pharmacology; D051379:Mice; D010703:Phorbol Esters / Q000494:pharmacology; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D011493:Protein Kinase C / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000378:metabolism; D011955:Receptors, Drug; D011971:Receptors, Immunologic / Q000032:analysis; D012964:Sodium / Q000378:metabolism; D010738:Type C Phospholipases / Q000494:pharmacology
D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D004075:Diglycerides; D007328:Insulin; D010703:Phorbol Esters; D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; D011955:Receptors, Drug; D011971:Receptors, Immunologic; C083141:phorbol ester binding protein; C027776:phorbol ester receptor; D004247:DNA; D012964:Sodium; D066246:ErbB Receptors; D011493:Protein Kinase C; D010738:Type C Phospholipases; D011188:Potassium