Arrestin

Arrestin

protein
Name = arrestin beta 1
caption =


width =
HGNCid = 711
Symbol = ARRB1
AltSymbols = ARR1
EntrezGene = 408
OMIM = 107940
RefSeq = NM_004041
UniProt = P49407
PDB =
ECnumber =
Chromosome = 11
Arm = q
Band = 13
LocusSupplementaryData =
protein
Name = arrestin beta 2
caption =


width =
HGNCid = 712
Symbol = ARRB2
AltSymbols = ARR2
EntrezGene = 409
OMIM = 107941
RefSeq = NM_004313
UniProt = P32121
PDB =
ECnumber =
Chromosome = 17
Arm = p
Band = 13
LocusSupplementaryData =
The arrestins are a family of proteins that are important for regulating signal transduction within cells. Arrestins are part of a conserved two step mechanism for regulating the activity of G-protein coupled receptors (GPCRs). In response to a stimulus, GPCRs activate a heterotrimeric G protein. In order to turn off this response, or adapt to a constant stimulus, activated receptors need to be silenced. The first step is phosphorylation by a class of serine/threonine kinases called G protein coupled receptor kinases (GRKs). This phosphorylation specifically marks the activated receptor for arrestin binding. Once arrestin is bound to the receptor it is unable to signal further. Recent research continues to expand the known actions of arrestins, which can bind to other classes of receptors and can directly activate signaling pathways on their own.

Different arrestins (visual arrestin (or Arrestin 1), beta-arrestin 1 (or Arrestin 2) and beta-arrestin 2 (or Arrestin 3) can reduce the activity of their target GPCRs in several different ways. The simplest mechanism for an arrestin to inhibit the activation of its target is for it to bind to the intracellular domain of the GPCR in such a way that the binding site for the heterotrimeric G-protein is blocked, preventing extra cellular signals from activating the pathway (desensitization). Another regulatory mechanism employed by arrestins is to link the receptor to elements of the membrane internalization machinery (clathrin mediated endocytosis) which leads to the internalization of the receptor in a coated vesicle that is going to fuse to an internal compartment, called endosome. Once in there, the receptor could be either targeted to degradation compartments (lysosomes) or recycled back to the plasma membrane where it will be once again competent for activation.

It has to be noted that at the steady state, beta arrestin is found in the cytoplasm of the cell in an inactive form, characterized by a 'close' 3D conformation. Upon activation and phosphorylation of the GPCR, the protein beta arrestin is recruited at the plasma membrane on the receptor, and activated by a conformational change characterized by a movement of its two globular domains and a released of its C-terminal tail that contains binding sites to the internalization machinery (clathrin, AP-2 complexes). The release of the C-terminal tail leads to the targeting of the beta arrestin/GPCR complexes into clathrin coated pit (internalization structure). The pit is then going to invaginates and finally forms a vesicle that will enter the cytoplasm of the cell. Activation of beta arrestin is crucial as it governs the capacities of the protein to interact with the GPCR and to target the GPCR in clathrin coated pits.

More and more, new functions of beta arrestins are discovered. Recently, it has been shown that beta-arrestin shuttle between nucleus and cytoplasm. The function of beta-arrestin in the nucleus is not yet well understood, even if some data indicate clearly that beta-arrestin enters and exit the nucleus to take out from there some of its partners like the kinase JNK3 or the ubiquitin ligase Mdm2. Those partners have a function in the nucleus, therefore, beta-arrestin, by exporting them outside the nucleus, inhibits their function. In the nucleus, it has also been described that beta arrestins are also able to modify gene expression, by enhancing transcription of some specific genes.

GPCRs form the largest family of receptors, involved in many processes like hormonal system regulation, cardiac regulation, pain, vision, taste, and almost all of them are downregulated by β-Arrestin 1 and/or 2. Beta-arrestin 2, for example, is responsible for the downregulation of β-Adrenergic receptor which is phosphorylated by the β-adrenergic receptor kinase, thyrotropin releasing hormone receptor (TRHR), C5a Receptor (C5aR), AngiotensinII receptor.

It should be noted that arrestins are produced endogenously within lots of cell type, are present in all eukaryotes, therefore conserved among evolution, and do not diffuse across cellular membranes.

External links

* http://www.nlm.nih.gov/cgi/mesh/2007/MB_cgi?mode=&term=ARRESTINS


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Look at other dictionaries:

  • arrestin — arrestin. См. аррестин. (Источник: «Англо русский толковый словарь генетических терминов». Арефьев В.А., Лисовенко Л.А., Москва: Изд во ВНИРО, 1995 г.) …   Молекулярная биология и генетика. Толковый словарь.

  • Arrestin — S Arrestin Größe 405 Aminosäuren Kofaktor Ca2+ Bezeichner …   Deutsch Wikipedia

  • arrestin — Family of inhibitory proteins that bind to tyrosine phosphorylated receptors, thereby blocking their interaction with G proteins and effectively terminating the signalling. Arrestin (S antigen; 48 kD, from retinal rods) competes with transducin… …   Dictionary of molecular biology

  • arrestin — ar·res·tin (ə resґtin) any of a family of inhibitory proteins that bind to phosphorylated G protein–coupled receptors and so block their interaction with G proteins. In the retina, arrestin binds activated phosphorylated rhodopsin and… …   Medical dictionary

  • Arrestin beta 2 — Arrestin, beta 2, also known as ARRB2, is a human gene that codes an intracellular protein β arrestin 2.Members of arrestin/beta arrestin protein family are thought to participate in agonist mediated desensitization of G protein coupled receptors …   Wikipedia

  • Arrestin beta 1 — Arrestin, beta 1, also known as ARRB1, is a human gene. [cite web | title = Entrez Gene: ARRB1 arrestin, beta 1| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene Cmd=ShowDetailView TermToSearch=408| accessdate = ] PBB Summary section title …   Wikipedia

  • arrestin — noun Any of a group of proteins that regulate signal transduction within cells …   Wiktionary

  • S-Arrestin — Masse/Länge Primärstruktur 405 Aminosäuren …   Deutsch Wikipedia

  • ARR3 — Arrestin 3, retinal (X arrestin), also known as ARR3, is a human gene.cite web | title = Entrez Gene: ARR3 arrestin 3, retinal (X arrestin)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene Cmd=ShowDetailView TermToSearch=407| accessdate =… …   Wikipedia

  • аррестин — arrestin аррестин. Белок сетчатки глаз, контролирующий светочувствительность родопсина <rhodopsin> путем связывания с ним; в геноме человека ген, кодирующий А., локализован на участке q24 37 хромосомы 2. (Источник: «Англо русский толковый… …   Молекулярная биология и генетика. Толковый словарь.

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