Activin type 2 receptors

The Activin type 2 receptors modulate signals for ligands belonging to the Transforming growth factor beta superfamily of ligands. These include: Activin (or Inhibin), Bone morphogenetic proteins and Nodal. They are involved in a host of physiological processes including, growth, cell differentiation, homeostasis, osteogenesis, apoptosis and many other functions. There are two Activin type two receptors: ACVR2A and ACVR2B.

Despite the large amount of processes that these ligands regulate, they all operate through essentially the same pathway: A ligand binds to a Type two receptor, which recruits and trans-phosphorylate a type I receptor. The type I receptor recruits a receptor regulated SMAD (R-SMAD) which it phosphorylates. The RSMAD then translocates to the nucleus where it functions as a transcription factor.

Functions

Several ligands that signal through the Activin type II receptors regulate muscle growthcite journal
last =
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authorlink =
coauthors = Lee SJ, Reed LA, Davies MV, Girgenrath S, Goad ME, Tomkinson KN, Wright JF, Barker C, Ehrmantraut G, Holmstrom J, Trowell B, Gertz B, Jiang MS, Sebald SM, Matzuk M, Li E, Liang LF, Quattlebaum E, Stotish RL, Wolfman NM
year = 2005
month = Dec
title = Regulation of muscle growth by multiple ligands signaling through activin type II receptors
journal = Proc Natl Acad Sci U S A.
volume = 102
issue = 50
page =
pages = 18117–22
article =
doi =
id = Entrez Pubmed|16330774
url =http://www.pnas.org/cgi/content/full/102/50/18117
format =
accessdate = ] . Myostatin, a TGF-beta superfamily member, is a negative regulator of muscle growth. Myostatin binds to ACVR2B and to a lesser extent ACVR2A. In mice that were ACVR2A ^-/- (null) mutants there was an increase in all four muscle groups studied (pectoralis, triceps, quadriceps, and gastrocnemious/plantaris muscles). Two of these muscle groups (pectoralis and triceps)were increased in ACVR2B ^-/- (null) mutants.

Activin plays a significant role in reproduction. ACVR2 receptors are present in the testis during testicular developmentcite journal
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coauthors = Anderson RA, Cambray N, Hartley PS, McNeilly AS.
year = 2002
month = Jun
title = Expression and localization of inhibin alpha, inhibin/activin betaA and betaB and the activin type II and inhibin beta-glycan receptors in the developing human testis
journal = Reproduction.
volume = 123
issue = 6
page =
pages =
article =
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id =
url =http://www.reproduction-online.org/cgi/reprint/123/6/779
format = pdf
accessdate = 2006-07-11 ] . ACR2A and ACVR2B was found to be localized primarily in the gonocytes as well as in sertoli cells. These cells are responsive to both autocrine and paracrine Activin B signaling, which controls their proliferation. Cells of the epididymis also have ACVR2A receptors present. ACVR2B receptors were found to be localized in the rete testis.

Disease

The ACVR2 gene is often found inactivated in prostate cancer and tumors with microsatellite instability.cite journal |author=Rossi MR, Ionov Y, Bakin AV, Cowell JK |title=Truncating mutations in the ACVR2 gene attenuates activin signaling in prostate cancer cells |journal=Cancer Genet. Cytogenet. |volume=163 |issue=2 |pages=123–9 |year=2005 |pmid=16337854 |doi=10.1016/j.cancergencyto.2005.05.007]

In the lab, it has been shown that truncated mutations in the ACVR2 gene causes a significant reduction in activin mediated cell signaling. In 58.1% of microsatellite unstable (MSI-H) colorectal cancers the ACVR2A gene has been found mutated. It also plays a role in non - MSI-H colorectal cancers.cite journal |author=Olaru A, Mori Y, Yin J, "et al" |title=Loss of heterozygosity and mutational analyses of the ACTRII gene locus in human colorectal tumors |journal=Lab. Invest. |volume=83 |issue=12 |pages=1867–71 |year=2003 |pmid=14691305 |doi=]

Related

* Stamulumab (MYO-029) Myostatin Inhibitor [http://www.mdausa.org/research/060106myostatin_blocker.html New Myostatin Blocker Makes Mouse Muscles 60 Percent Larger] , MDA Research News, January 6, 2006]

References

Category:S/T domain