Mechanisms of action of cell growth-promoting peptides and polypeptides: role for inositol lipid hydrolysis.
Brown K.D.
The interaction of growth factors with their cell surface receptors initiates a series of events that ultimately bring about DNA synthesis and cell proliferation. There is increasing evidence that, at least for some factors, membrane inositol lipids may provide the second messengers that convey information from the cell surface to the nucleus. The exposure of Swiss 3T3 mouse embryo cells to several peptide and polypeptide growth-promoting agents results in a rapid increase in the hydrolysis of phosphatidylinositol 4,5-bisphosphate to inositol 1,4,5-trisphosphate and diacylglycerol, both of which function as second messengers: the former induces the release of Ca++ from intracellular stores, and the latter is a potent activator of protein kinase C. Activation of protein kinase C causes a stimulation of Na-H exchange across the cell membrane and a consequent increase in intracellular pH. The contribution of these ionic events to the control of gene expression and the stimulation of DNA synthesis remains unknown.
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