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

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. The best-known family of G protein-coupled receptors (GPCRs) contains a conserved structural motif, consisting of seven α-helical membrane-spanning regions; thus, they are also frequently referred to as heptahelical or serpentine receptors. These receptors participate in a broad range of important biological functions, such as photo- and chemoreception, neurotransmission, regulated secretion from endocrine and exocrine glands, blood pressure control, platelet function, chemotaxis, exocytosis, embryogenesis, angiogenesis, tissue regeneration, and control of normal cell growth. Furthermore, they are also implicated in a number of disease states and are estimated to be the target for more than half of all drugs currently available. Initial studies established that these receptors affect the generation of small molecules that act as intracellular mediators or second messengers. However, recent work has revealed that a growing family of protein kinases, collectively known as extracellular signal-regulated kinases (ERKs) or mitogen-activated protein kinases (MAPKs), plays a central role in transmitting signals from extracellular stimuli to the nucleus. Such signals affect the expression of genes whose products influence many biological processes, including normal and aberrant cell growth. It is now becoming evident that GPCRs transduce signals to the nucleus through a highly interconnected network of biochemical routes that can regulate the activity of members of the MAPK superfamily. This knowledge affords a unique opportunity to begin unraveling the intricacies of how these cell surface receptors affect a very fine balance of nuclear regulatory molecules that control gene expression. Understanding how subtle perturbation of this signaling network can result in pathological situations provides golden opportunities to identify novel molecular targets for pharmacological intervention in a variety of diseases.

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Classifications


Resource Type: Bibliography, Diagram, Illustration, Journal article/Issue, Review
Audience Level: Undergraduate upper division 15-16, Graduate, Professional (degree program)

Author and Copyright


Authors and Editors: J. Silvio Gutkind of National Institute of Dental Research, National Institutes of Health
Publisher: American Association for the Advancement of Science
Format: application/pdf, image/gif, image/jpeg, text/html
Copyright and other restrictions: Yes
Cost: Yes

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Collection:
STKE/Science Signaling


     
   

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