Activin type 2 receptors
| activin A receptor, type IIA | |
|---|---|
| Identifiers | |
| Symbol | ACVR2A |
| Alt. symbols | ACVR2 |
| Entrez | 92 |
| HUGO | 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 |
| Entrez | 93 |
| HUGO | 174 |
| OMIM | 602730 |
| RefSeq | NM_001106 |
| UniProt | Q13705 |
| Other data | |
| Locus | Chr. 3 p22 |
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-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 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]
Clinical significance
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]
Inhibitors
- Stamulumab (MYO-029) Myostatin Inhibitor[5]
References
- ↑ 1.0 1.1 1.2 1.3 Lua error in package.lua at line 80: module 'strict' not found.
- ↑ 2.0 2.1 2.2 2.3 Lua error in package.lua at line 80: module 'strict' not found.
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- ↑ New Myostatin Blocker Makes Mouse Muscles 60 Percent Larger, MDA Research News, January 6, 2006
