Overexpression of pp60c-src is associated with altered regulation of adenylyl cyclase.

Published

Journal Article

The ability of activators of the beta-adrenergic receptor to elevate intracellular cAMP levels in murine fibroblasts is enhanced upon overexpression of avian c-src [Bushman et al. (1990) Proc. natn. Acad. Sci. U.S.A. 87, 7462-7466]. To investigate the molecular basis for this effect, we prepared particulate fractions from control and pp60c-src overexpressing C3H10T1/2 fibroblasts and assessed the relative abilities of several activators of the beta-adrenergic receptor-Gs-adenylyl cyclase (AC) signal transduction pathway to stimulate the enzymatic response. Two- to three-fold increases in both the sensitivity and maximum responsiveness of AC to the beta-adrenergic agonist isoproterenol were consistently observed in fractions prepared from the c-src overexpressing cells. Interestingly, the AC response to two agents believed to act directly at the level of the G protein were either enhanced (NaF) or unaffected (GTP gamma S) by c-src overexpression. Finally, overexpression of c-src was associated with a reduced ability of both Mn2+ and forskolin to activate AC directly. These results suggest that overexpression of wild type c-src may affect two distinct steps in the regulation of AC exerting a positive effect at the level of Gs activation and a negative effect on AC itself. As no differences in the relative number or affinity of beta-adrenergic receptors, or in the level of AC, Gs alpha or G beta, were detected between control cells and those overexpressing c-src, we propose that pp60c-src overexpression results in a modification of one or more components in this signal transduction pathway.

Full Text

Duke Authors

Cited Authors

  • Luttrell, DK; Hausdorff, WP; Moyers, JE; Gilmer, TM; Parsons, SJ; Caron, MG; Lefkowitz, RJ

Published Date

  • September 1992

Published In

Volume / Issue

  • 4 / 5

Start / End Page

  • 531 - 541

PubMed ID

  • 1384635

Pubmed Central ID

  • 1384635

International Standard Serial Number (ISSN)

  • 0898-6568

Language

  • eng

Conference Location

  • England