This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kacich, R. L. Articles by Coughlin, S. R. Search for Related Content PubMed PubMed Citation Articles by Kacich, R. L. Articles by Coughlin, S. R.

Arachidonic Acid and Cyclic Adenosine Monophosphate Stimulation of c-fos Expression bya Pathway Independent of Phorbol Ester-Sensitive Protein Kinase C

Howard Hughes Medical Institute, Cardiovascular Research Institute and Department of Medicine, University of California San Francisco, California 94143

Address requests for reprints to: Lewis T. Williams, M.D., Ph.D., University of California, San Francisco, Howard Hughes Medical Institute, U-426, 533 Parnassus Avenue, Box 0724, San Francisco, California 94143.

Abstract

The stimulation of cell proliferation by platelet-derived and other growth factors is associated with a rapid increase in the expression of the c-fos protooncogene. We and others have shown that phosphosphoinositide turnover and protein kinase C play a role in the activation of this gene by growth factors, but that a second, kinase C-independent pathway(s) exist. Because cAMP potentiates the actions of a number of growth factors and is elevated in plateletderived growth factor-stimulated Swiss 3T3 cells, we examined the ability of cAMP to stimulate c-fos expression in this cell type. Forskolin, a direct activator of adenylate cyclase, elicited marked increases in c-fos mRNA levels. Receptor-mediated activation of adenylate cyclase by prostaglandin E₁ and stimulation with the cAMP analog 8-bromo-cAMP also enhanced c-fos expression. In cells made protein-kinase C deficient, c-fos induction by phorbol ester was abolished; by contrast, c-fos was still induced by cAMP-elevating agents in protein kinase C-depleted cells. Platelet-derived growth factor causes cAMP accumulation by stimulating arachidonic acid release and the formation of prostaglandins capable of activating adenylate cyclase. The addition of arachidonic acid and the arachidonate metabolite prostaglandin E₂ to Swiss 3T3 cultures stimulated c-fos expression. These data suggest the existence of a pathway from growth factor receptor to gene induction that is mediated by cAMP and does not depend on a phorbol ester-sensitive protein kinase C.

FOOTNOTES

This work was supported by NIH Grant RO1-HL-32898 and by National Research Service Award HL-07453-02.

Received for publication October 2, 1987. Accepted for publication November 1, 1987.

This article has been cited by other articles:

				K. Chakraborty, P. C. Maity, A. K. Sil, Y. Takeda, and S. Das cAMP Stringently Regulates Human Cathelicidin Antimicrobial Peptide Expression in the Mucosal Epithelial Cells by Activating cAMP-response Element-binding Protein, AP-1, and Inducible cAMP Early Repressor J. Biol. Chem., August 14, 2009; 284(33): 21810 - 21827. [Abstract] [Full Text] [PDF]