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

Publication ,  Journal Article
Luttrell, DK; Hausdorff, WP; Moyers, JE; Gilmer, TM; Parsons, SJ; Caron, MG; Lefkowitz, RJ
Published in: Cell Signal
September 1992

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.

Duke Scholars

Published In

Cell Signal

DOI

ISSN

0898-6568

Publication Date

September 1992

Volume

4

Issue

5

Start / End Page

531 / 541

Location

England

Related Subject Headings

  • Signal Transduction
  • Receptors, Adrenergic, beta
  • Proto-Oncogene Proteins pp60(c-src)
  • Mice
  • Isoproterenol
  • GTP-Binding Proteins
  • Enzyme Activation
  • Cyclic AMP
  • Cell Line
  • Biochemistry & Molecular Biology
 

Citation

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Luttrell, D. K., Hausdorff, W. P., Moyers, J. E., Gilmer, T. M., Parsons, S. J., Caron, M. G., & Lefkowitz, R. J. (1992). Overexpression of pp60c-src is associated with altered regulation of adenylyl cyclase. Cell Signal, 4(5), 531–541. https://doi.org/10.1016/0898-6568(92)90022-z
Luttrell, D. K., W. P. Hausdorff, J. E. Moyers, T. M. Gilmer, S. J. Parsons, M. G. Caron, and R. J. Lefkowitz. “Overexpression of pp60c-src is associated with altered regulation of adenylyl cyclase.Cell Signal 4, no. 5 (September 1992): 531–41. https://doi.org/10.1016/0898-6568(92)90022-z.
Luttrell DK, Hausdorff WP, Moyers JE, Gilmer TM, Parsons SJ, Caron MG, et al. Overexpression of pp60c-src is associated with altered regulation of adenylyl cyclase. Cell Signal. 1992 Sep;4(5):531–41.
Luttrell, D. K., et al. “Overexpression of pp60c-src is associated with altered regulation of adenylyl cyclase.Cell Signal, vol. 4, no. 5, Sept. 1992, pp. 531–41. Pubmed, doi:10.1016/0898-6568(92)90022-z.
Luttrell DK, Hausdorff WP, Moyers JE, Gilmer TM, Parsons SJ, Caron MG, Lefkowitz RJ. Overexpression of pp60c-src is associated with altered regulation of adenylyl cyclase. Cell Signal. 1992 Sep;4(5):531–541.
Journal cover image

Published In

Cell Signal

DOI

ISSN

0898-6568

Publication Date

September 1992

Volume

4

Issue

5

Start / End Page

531 / 541

Location

England

Related Subject Headings

  • Signal Transduction
  • Receptors, Adrenergic, beta
  • Proto-Oncogene Proteins pp60(c-src)
  • Mice
  • Isoproterenol
  • GTP-Binding Proteins
  • Enzyme Activation
  • Cyclic AMP
  • Cell Line
  • Biochemistry & Molecular Biology