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]
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]
^Rossi MR, Ionov Y, Bakin AV, Cowell JK (December 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. PMID16337854.
