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Sci. STKE, 11 July 2000
Vol. 2000, Issue 40, p. re1
[DOI: 10.1126/stke.2000.40.re1]


Regulation of Mitogen-Activated Protein Kinase Signaling Networks by G Protein-Coupled Receptors

J. Silvio Gutkind

Oral and Pharyngeal Cancer Branch, National Institute of Dental Research, National Institutes of Health, 30 Convent Drive, Building 30, Room 212, Bethesda, MD 20892-4330, USA. E-mail: sg39v{at}

Abstract: The family of receptors that transmit signals through the activation of heterotrimeric GTP-binding proteins (G proteins) constitutes the largest group of cell surface proteins involved in signal transduction. These receptors participate in a broad range of important biological functions and are implicated in a number of disease states. More than half of all drugs currently available influence G protein-coupled receptors (GPCRs). These receptors affect the generation of small molecules that act as intracellular mediators or second messengers, and can regulate a highly interconnected network of biochemical routes controlling the activity of several members of the mitogen-activated protein kinase (MAPK) superfamily. They include extracellular signal-regulated kinase 1 (ERK1) and ERK2 (or p44MAPK and p42MAPK), c-Jun NH2-terminal kinases (JNKs), ERK5 (or BMK), and p38 MAPKs, including p38α (or CSBP-1), p38β, p38{gamma} (or SAPK3 or ERK6), and p38{delta}?(or SAPK4). This review will focus on the molecular mechanisms by which GPCRs signal to the nucleus through this intricate network of second messenger-generating systems and MAPK signaling pathways, thereby affecting the expression of genes whose products influence many biological processes, including normal and aberrant cell growth.

Citation: J. S. Gutkind, Regulation of Mitogen-Activated Protein Kinase Signaling Networks by G Protein-Coupled Receptors. Sci. STKE 2000, re1 (2000).

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