These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Differential regulation of extracellular signal-regulated protein kinases (ERKs) 1 and 2 by cAMP and dissociation of ERK inhibition from anti-mitogenic effects in rabbit vascular smooth muscle cells.
    Author: Cospedal R, Lobo M, Zachary I.
    Journal: Biochem J; 1999 Sep 01; 342 ( Pt 2)(Pt 2):407-14. PubMed ID: 10455028.
    Abstract:
    The inhibition of extracellular signal-regulated protein kinases (ERKs) is implicated in the negative regulation of vascular smooth muscle cell (VSMC) mitogenesis by cAMP-elevating agents and transforming growth factor beta(1) (TGF-beta(1)). These factors inhibited rabbit aortic VSMC mitogenesis induced by platelet-derived growth factor (PDGF)-BB by preventing the entry of cells into S-phase. cAMP-elevating agents partly inhibited the late phase (1-4 h) of activation of ERKs 1 and 2 induced by PDGF-BB without inhibiting the early phase of activity (5-15 min) and had no effect on activity induced by basic fibroblast growth factor (bFGF). In contrast, cAMP elevation caused a marked inhibition of early ERK activation induced by angiotensin II and thrombin. TGF-beta(1) had no inhibitory effect on ERK activation induced by PDGF-BB or bFGF. The inhibition of PDGF-BB-stimulated DNA synthesis by either forskolin/3-isobutyl-1-methylxanthine (IBMX) or TGF-beta(1) was not decreased when the agents were added up to 8 h after growth factor. In contrast, the selective ERK kinase inhibitor PD98059 was a weak inhibitor of DNA synthesis; a combination of PD98059 and forskolin/IBMX had an additive inhibitory effect on DNA synthesis. Forskolin/IBMX inhibited the growth factor-induced expression of c-myc mRNA and cyclin D(1) protein, and enhanced the protein expression of p27(kip1). TGF-beta(1) had no effect on the expression of c-myc or p27(kip1) and weakly attenuated the expression of cyclin D(1). These findings support the conclusion that the suppression of VSMC mitogenesis by cAMP and TGF-beta(1) is independent of ERK inhibition. Anti-mitogenic effects of cAMP might be primarily mediated by events in late G(1).
    [Abstract] [Full Text] [Related] [New Search]