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Seven-Transmembrane Receptor Signaling Through {beta}-Arrestin

Cell surface receptors are important communicators of external stimuli to the cell interior where they lead to initiation of various signaling pathways and cellular responses. The largest receptor family is the seven-transmembrane receptor (7TMR) family, with approximately 1000 coding genes in the human genome. When 7TMRs are stimulated with agonists, they activate heterotrimeric guanine nucleotide-binding proteins (G proteins), leading to the production of signaling second messengers, such as adenosine 3′,5′-monophosphate, inositol phosphates, and others. Activated receptors are rapidly phosphorylated on serine and threonine residues by specialized enzymes called G protein–coupled receptor kinases. Phosphorylated receptors bind the multifunctional adaptor proteins β-arrestin1 and β-arrestin2 with high affinity. β-arrestin binding blocks further G protein coupling, leading to "desensitization" of G protein–dependent signaling pathways. For several years, this was considered the sole function of β-arrestins. However, novel functions of β-arrestins have been discovered. β-arrestins are now designated as important adaptors that link receptors to the clathrin-dependent pathway of internalization. β-arrestins bind and direct the activity of several nonreceptor tyrosine kinases in response to 7TMR stimulation. β-arrestins also bind and scaffold members of such signaling cascades as the mitogen-activated protein kinases (MAPKs). β-arrestins are crucial components in 7TMR signaling leading to cellular responses that include cell survival and chemotaxis. β-arrestins act as endocytic adaptors and signal mediators not only for the 7TMRs, but also for several receptor tyrosine kinases.

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

Author and Copyright


Authors and Editors: Sudha K. Shenoy of Department of Medicine, Howard Hughes Medical Institute, Robert J. Lefkowitz of Department of Medicine, Duke University Medical Center
Publisher: American Association for the Advancement of Science
Format: application/pdf, image/gif, image/jpeg, image/svg+xml, text/html
Copyright and other restrictions: Yes
Cost: No

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