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
[edit | edit source]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
[edit | edit source]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
[edit | edit source]- Stamulumab (MYO-029) myostatin Inhibitor[5]
References
[edit | edit source]- ^ a b c d Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
- ^ a b c d Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
- ^ Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
- ^ Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
- ^ New Myostatin Blocker Makes Mouse Muscles 60 Percent Larger Archived 2007-09-27 at the Wayback Machine, MDA Research News, January 6, 2006