Seven-transmembrane receptor signaling through beta-arrestin.

Published online

Journal Article (Review)

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 beta-arrestin1 and beta-arrestin2 with high affinity. Beta-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 beta-arrestins. However, novel functions of beta-arrestins have been discovered. Beta-arrestins are now designated as important adaptors that link receptors to the clathrin-dependent pathway of internalization. Beta-arrestins bind and direct the activity of several nonreceptor tyrosine kinases in response to 7TMR stimulation. Beta-arrestins also bind and scaffold members of such signaling cascades as the mitogen-activated protein kinases (MAPKs). Beta-arrestins are crucial components in 7TMR signaling leading to cellular responses that include cell survival and chemotaxis. Beta-arrestins act as endocytic adaptors and signal mediators not only for the 7TMRs, but also for several receptor tyrosine kinases.

Full Text

Duke Authors

Cited Authors

  • Shenoy, SK; Lefkowitz, RJ

Published Date

  • November 1, 2005

Published In

Volume / Issue

  • 2005 / 308

Start / End Page

  • cm10 -

PubMed ID

  • 16267056

Pubmed Central ID

  • 16267056

Electronic International Standard Serial Number (EISSN)

  • 1525-8882

Digital Object Identifier (DOI)

  • 10.1126/stke.2005/308/cm10

Language

  • eng

Conference Location

  • United States