Mitogenic signaling pathways induced by G protein-coupled receptors
Article first published online: 4 SEP 2007
Copyright © 2007 Wiley-Liss, Inc.
Journal of Cellular Physiology
Volume 213, Issue 3, pages 589–602, December 2007
How to Cite
Rozengurt, E. (2007), Mitogenic signaling pathways induced by G protein-coupled receptors. J. Cell. Physiol., 213: 589–602. doi: 10.1002/jcp.21246
- Issue published online: 26 SEP 2007
- Article first published online: 4 SEP 2007
- Manuscript Accepted: 11 JUL 2007
- Manuscript Received: 10 JUL 2007
- National Institutes of Health. Grant Numbers: R0-1 DK 55003, R0-1 DK56930, P30 DK41301
G protein-coupled receptor (GPCR) agonists, including neurotransmitters, hormones, chemokines, and bioactive lipids, act as potent cellular growth factors and have been implicated in a variety of normal and abnormal processes, including development, inflammation, and malignant transformation. Typically, the binding of an agonistic ligand to its cognate GPCR triggers the activation of multiple signal transduction pathways that act in a synergistic and combinatorial fashion to relay the mitogenic signal to the nucleus and promote cell proliferation. A rapid increase in the activity of phospholipases C, D, and A2 leading to the synthesis of lipid-derived second messengers, Ca2+ fluxes and subsequent activation of protein phosphorylation cascades, including PKC/PKD, Raf/MEK/ERK, and Akt/mTOR/p70S6K is an important early response to mitogenic GPCR agonists. The EGF receptor (EGFR) tyrosine kinase has emerged as a transducer in the signaling by GPCRs, a process termed transactivation. GPCR signal transduction also induces striking morphological changes and rapid tyrosine phosphorylation of multiple cellular proteins, including the non-receptor tyrosine kinases Src, focal adhesion kinase (FAK), and the adaptor proteins CAS and paxillin. The pathways stimulated by GPCRs are extensively interconnected by synergistic and antagonistic crosstalks that play a critical role in signal transmission, integration, and dissemination. The purpose of this article is to review recent advances in defining the pathways that play a role in transducing mitogenic responses induced by GPCR agonists. J. Cell. Physiol. 213:589–602. © 2007 Wiley-Liss, Inc.