Activin type 2 receptors

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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.

Contents

Functions

Several ligands that signal through the Activin type II receptors regulate muscle growth1. Myostatin, a TGF-beta superfamily member, is a negative regulator of muscle growth1. 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)1. Two of these muscle groups (pectoralis and triceps)were increased in ACVR2B -/- (null) mutants1.

Activin plays a significant role in reproduction. ACVR2 receptors are present in the testis during testicular development2. ACR2A and ACVR2B was found to be localized primarily in the gonocytes as well as in sertoli cells2. These cells are responsive to both autocrine and paracrine Activin B signaling, which controls their proliferation2. Cells of the epididymis also have ACVR2A receptors present. ACVR2B receptors were found to be localized in the rete testis2.

Disease

The ACVR2 gene is often found inactivated in prostate cancer and tumors with microsatellite instability.3

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.4

Related

References

  1. ^ a b c d "Regulation of muscle growth by multiple ligands signaling through activin type II receptors". Proc Natl Acad Sci U S A. 102 (50): 18117–22. December 2005. Entrez PubMed 16330774, http://www.pnas.org/cgi/content/full/102/50/18117. 
  2. ^ a b c d "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" (pdf). Reproduction. 123 (6). June 2002, http://www.reproduction-online.org/cgi/reprint/123/6/779. Retrieved on 11 July 2006. 
  3. ^ Rossi MR, Ionov Y, Bakin AV, Cowell JK (2005). "Truncating mutations in the ACVR2 gene attenuates activin signaling in prostate cancer cells". Cancer Genet. Cytogenet. 163 (2): 123–9. doi:10.1016/j.cancergencyto.2005.05.007. PMID 16337854. 
  4. ^ Olaru A, Mori Y, Yin J, et al (2003). "Loss of heterozygosity and mutational analyses of the ACTRII gene locus in human colorectal tumors". Lab. Invest. 83 (12): 1867–71. PMID 14691305. 
  5. ^ New Myostatin Blocker Makes Mouse Muscles 60 Percent Larger, MDA Research News, January 6, 2006
v • d • e
Cell signaling: TGF beta signaling pathway
TGF beta superfamily of ligands
TGF beta receptors
(Activin, BMP)
TGFBR1: Activin type 1 receptors (ACVR1, ACVR1B, ACVR1C) - ACVRL1 - BMPR1 (BMPR1A - BMPR1B)

TGFBR2: Activin type 2 receptors (ACVR2A, ACVR2B) - AMHR2 - BMPR2

TGFBR3: betaglycan
Transducers/SMAD
Ligand inhibitors
Coreceptors
Other
v • d • e
Receptors: growth factor receptors
Nerve growth factors
Somatomedin
CSF
TGF pathway
Other

Wikipedia content modification information:

  • This page was last modified on 17 October 2008, at 06:56.

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