A role for phospholipase D in control of mitogenesis

How do growth factors that act on G protein-coupled cell-surface receptors communicate with the nucleus? These receptors commonly activate phospholipase C, and it has been assumed that the consequent rise in cytosolic Ca2+ concentrations and activation of protein kinase C mediates the mitogenic response. Recent evidence has demonstrated that phospholipase D (PLD) might be capable of eliciting mitogenesis. This enzyme is stimulated by a variety of growth factors, including those that act on receptors that possess intrinsic tyrosine kinase activity as well as those acting on G protein-coupled receptors. In this review, Michael Boarder considers the evidence that PLD, activated downstream of tyrosine protein kinases by both classes of cell-surface growth factor receptor, is implicated in the mitogenic response. This evidence is related to the possibility of PLD involvement in the regulation of vascular smooth muscle cell proliferation by endothelin-1 and platelet-derived growth factor.