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.
Activin plays a significant role in reproduction. ACVR2 receptors are present in the testis during testicular development. ACR2A and ACVR2B was found to be localized primarily in the gonocytes as well as in sertoli cells. These cells are responsive to both autocrine and paracrine Activin B signaling, which controls their proliferation. Cells of the epididymis also have ACVR2A receptors present. ACVR2B receptors were found to be localized in the rete testis.
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.
^ abcdAnderson RA, Cambray N, Hartley PS, McNeilly AS (June 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". Reproduction123 (6): 779–88. doi:10.1530/rep.0.1230779. PMID12052232.
^Olaru A, Mori Y, Yin J, Wang S, Kimos MC, Perry K, Xu Y, Sato F, Selaru FM, Deacu E, Sterian A, Shibata D, Abraham JM, Meltzer SJ (December 2003). "Loss of heterozygosity and mutational analyses of the ACTRII gene locus in human colorectal tumors". Lab. Invest.83 (12): 1867–71. doi:10.1097/01.LAB.0000106723.75567.72. PMID14691305.