Biology:Activin type 2 receptors
| activin A receptor, type IIA | |
|---|---|
| Identifiers | |
| Symbol | ACVR2A |
| Alt. symbols | ACVR2 |
| NCBI gene | 92 |
| HGNC | 173 |
| OMIM | 102581 |
| RefSeq | NM_001616 |
| UniProt | P27037 |
| Other data | |
| Locus | Chr. 2 q22.2-23.3 |
| activin A receptor, type IIB | |
|---|---|
| Identifiers | |
| Symbol | ACVR2B |
| NCBI gene | 93 |
| HGNC | 174 |
| OMIM | 602730 |
| RefSeq | NM_001106 |
| UniProt | Q13705 |
| Other data | |
| Locus | Chr. 3 p22 |
The activin type 2 receptors belong to a larger TGF-beta receptor family and modulate signals for transforming growth factor beta ligands. These receptors 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 2 receptor, which recruits and trans-phosphorylates 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.
Function
Several ligands that signal through the activin type 2 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]
Clinical significance
The ACVR2 gene is often found inactivated in prostate cancer and tumors with microsatellite instability.[3]
In a 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]
Inhibitors
- Stamulumab (MYO-029) myostatin Inhibitor[5]
References
- ↑ 1.0 1.1 1.2 1.3 "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. doi:10.1073/pnas.0505996102. PMID 16330774. Bibcode: 2005PNAS..10218117L.
- ↑ 2.0 2.1 2.2 2.3 "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". Reproduction 123 (6): 779–88. June 2002. doi:10.1530/rep.0.1230779. PMID 12052232.
- ↑ "Truncating mutations in the ACVR2 gene attenuates activin signaling in prostate cancer cells". Cancer Genet. Cytogenet. 163 (2): 123–9. December 2005. doi:10.1016/j.cancergencyto.2005.05.007. PMID 16337854.
- ↑ "Loss of heterozygosity and mutational analyses of the ACTRII gene locus in human colorectal tumors". Lab. Invest. 83 (12): 1867–71. December 2003. doi:10.1097/01.LAB.0000106723.75567.72. PMID 14691305.
- ↑ New Myostatin Blocker Makes Mouse Muscles 60 Percent Larger , MDA Research News, January 6, 2006
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