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.
[edit] Functions
Several ligands that signal through the Activin type II receptors regulate muscle growth[1]. Myostatin, a tgf beta superfamily member, is a negative regulator of muscle growth[1]. 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) mutants[1].
Activin plays a significant role in reproduction. ACVR2 receptors are present in the testis during testicular development[2]. ACR2A and ACVR2B was found to be localized primarily in the gonocytes as well as in sertoli cells[2]. These cells are responsive to both autocrine and paracrine Activin B signaling, which controls their proliferation[2]. Cells of the epididymis also have ACVR2A receptors present. ACVR2B receptors were found to be localized in the rete testis[2].
[edit] 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[4]. 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[5].
[edit] References
- ^ a b c d (Dec 2005) "Regulation of muscle growth by multiple ligands signaling through activin type II receptors". Proc Natl Acad Sci U S A. 102 (50): 18117-22. Entrez PubMed 16330774.
- ^ a b c d (Jun 2002) "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). Retrieved on 2006-07-11.
- ^ Rossi, MR; Ionov Y, Bakin AV, Cowell JK. (Dec 2005). "Truncating mutations in the ACVR2 gene attenuates activin signaling in prostate cancer cells". Cancer Genet Cytogenet. 163 (2): 123-9.. Entrez PubMed 16337854.
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- ^ (Dec 2003) "Loss of heterozygosity and mutational analyses of the ACTRII gene locus in human colorectal tumors". Lab Invest. 83 ((12):). Entrez PubMed 14691305.
TGF beta superfamily of ligands:
Activin A and B - Anti-müllerian hormone - Bone morphogenetic proteins (BMP2, BMP3, BMP4, BMP5, BMP6, BMP7, BMP8a, BMP8b, BMP10 , BMP15) - Growth differentiation factors (GDF1, GDF2, GDF3, GDF5, GDF6, GDF7, GDF9, GDF10, GDF11, GDF15) - Inhibin A and B - Myostatin - Nodal - TGF beta family (TGF-β1, TGF-β2, TGF-β3)
Type II receptors:ACVR2A - ACVR2B - AMHR2 - BMPR2 - TGFBR2 - TGFBR3
Type I receptors: ACVR1A - ACVR1B - ACVR1C - ACVRL1 - BMPR1A - BMPR1B - TGFBR1
Signal transducers/SMAD: R-SMAD (SMAD1, SMAD2, SMAD3, SMAD5, SMAD9) - I-SMAD (SMAD6, SMAD7) - SMAD4
Ligand Inhibitors: Cerberus - Chordin - DAN - Decorin - Follistatin - Gremlin - Lefty - LTBP1 - Noggin - THBS1
