Modulation of prostaglandin G/H synthase expression in mesangial cells transfected by pp60c-src proto-oncogene

Experimental Cell Research
C O ReiserM Goppelt-Struebe

Abstract

The role of the protein tyrosine kinase pp60c-src in the expression of prostaglandin G/H synthase (PGHS), the key enzyme of prostaglandin synthesis, was investigated in rat renal mesangial cells. Transfection of mesangial cells with the proto-oncogene c-src resulted in nontransformed cells with constitutively enhanced pp60c-src kinase activity. As a control, mesangial cells were transfected with inactive pp60c-src, mutated in position 295 (lysine replaced by methionine). Expression of the constitutive isoform PGHS-1 was enhanced in cells overexpressing wild-type c-src compared to cells transfected with the kinase negative c-src mutant. Levels of other constitutively expressed proteins such as GAPDH and beta-actin were also enhanced. PGHS-2 was barely detectable in resting cells but was inducible by PDGF-AB, PDGF-BB, serotonin, FCS, and calcium ionophore A23187. Induction was diminished in pp60c-src kinase-overexpressing cells, independent of the stimulus used, suggesting interference at a late step in the signaling cascade. No induction of PGHS-2 mRNA was observed in mesangial cells transformed by the oncogene v-src. An increase in intracellular calcium levels is an early step in signal transduction by PDGF and serotonin in mes...Continue Reading

Citations

Feb 7, 2002·The Biochemical Journal·Angelika HahnMargarete Goppelt-Struebe
May 3, 2006·Vision Research·Lucy A Newman, Phyllis R Robinson
Jan 1, 1997·Journal of Lipid Mediators and Cell Signalling·C O Reiser, M Goppelt-Struebe
Aug 24, 2001·Journal of the American Society of Nephrology : JASN·Juliane Heusinger-RibeiroMargarete Goppelt-Struebe

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