Type I A-Kinase Is Activated by Platelet-Derived Growth Factor in Mesangial Cells☆

Abstract In the glomerular mesangial cell, platelet-derived growth factor (PDGF) activates several signal transduction pathways. We examined the effect of PDGF on cAMP production and on cAMP-dependent protein kinase (A-kinase) activation. In mesangial cells, PDGF stimulated cAMP production in a dose- and time-dependent manner. This effect of PDGF was not prevented by pre-incubation with 50 μM indomethicin. PDGF also activated type I A-kinase, the predominate A-kinase isoform in mesangial cells, measured either by a decrease in A-kinase photoaffinity labeling with 8-azido-[ 32 P]-cAMP, or by an increase in A-kinase substrate phosphorylation. The activation of A-kinase by PDGF is not dependent on the intermediate production of prostaglandins or cGMP. These data suggest that A-kinase participates in PDGF-induced signaling events in mesangial cells.