Platelet-derived growth factor stimulates de-novo synthesis of mitogen-activated protein kinase in renal mesangial cells .

Huwiler A ; Fabbro D ; Pfeilschifter J

Department of Pharmacology , University of Basel , Switzerland .

Eur J Biochem 227 : 209-13 ( 1995)

Abstract
Platelet-derived growth factor ( PDGF ) BB is a potent mitogen for renal mesangial cells and stimulates a biphasic mitogen-activated protein kinase ( MAP kinase ) activation . A rapid increase in activity ( maximal at min ) is followed by a lower persistent level of activity which is maximal at 4-6 h . The second peak of MAP kinase activity is markedly attenuated by the protein synthesis inhibitor cycloheximide and , consequently , is paralleled by a marked de-novo synthesis of p42 and p44 MAP kinases , as measured by immunoprecipitation of [ 35S]methionine-labeled mesangial cells and by a 700% increase in total MAP kinase protein , as detected by Western-blot analysis . A 30-min treatment with PDGF-BB is sufficient to induce pronounced de-novo synthesis of MAP kinase . However , for maximal induction of MAP kinase synthesis , PDGF is required to be present for at least 4 h . In addition , an increased de-novo synthesis of MAP kinase kinase , the upstream activator of MAP kinase , is observed in response to PDGF stimulation . We propose that PDGF-induced de-novo synthesis of MAP kinase and MAP kinase kinase is important for the potent mitogenic activity of this growth factor .