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

Huwiler, A.; Fabbro, D.; Pfeilschifter, J.

European Journal of Biochemistry 227(1-2): 209-213

1995


ISSN/ISBN: 0014-2956
PMID: 7851388
DOI: 10.1111/j.1432-1033.1995.tb20378.x
Accession: 009206469

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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 10 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.

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