Activin type 2 receptors

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Activin receptor type-2A Other names: Activin receptor type IIA, ACTR-IIA, ACTRIIA Genetic data Gene code: HUGO code:ACVR1 Protein Structure/Function Protein type: Serine/Threonine receptor kinase Domains: TS domain, S/T domain Other Taxa expressing: Homo sapiens; homologs: many metazoan phyla Cell types: many Subcellular localization: Plasma membrane Enzymatic Data Catalytic activity: ATP + (receptor-protein) = ADP + (receptor-protein) phosphate Cofactor(s): Magnesium or manganese Medical/Biotechnological data Diseases: -

Activin receptor type 1B Other names: Activin receptor type IIB, ACTR-IIB Genetic data Gene code: HUGO code: ACVR1B Protein Structure/Function Protein type: Serine/Threonine receptor kinase Domains: TS domain, S/T domain Other Taxa expressing: Homo sapiens; homologs: many metazoan phyla Cell types: many Subcellular localization: Plasma membrane Enzymatic Data Catalytic activity: ATP + (receptor-protein) = ADP + (receptor-protein) phosphate Cofactor(s): Magnesium or manganese

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-phosphorylate 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.

Contents 1 Functions 2 ACVR2A 2.1 Disease 3 ACVR2B 4 References

[edit] Functions

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].

[edit] ACVR2A

[edit] Disease

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^[4]. 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^[5].

Identifiers
Symbol(s)	ACVR2A ACVR2
Entrez	92
OMIM	102581
RefSeq	NM_001616
UniProt	P27037
Other data
Locus	Chr. 2 q22.2-23.3

[edit] ACVR2B

Identifiers
Symbol(s)	ACVR2B
Entrez	93
OMIM	602730
RefSeq	NM_001106
UniProt	Q13705
Other data
Locus	Chr. 3 p22

[edit] References

1. ^ ^{a b c d} (Dec 2005) "Regulation of muscle growth by multiple ligands signaling through activin type II receptors". Proc Natl Acad Sci U S A. 102 (50): 18117-22. Entrez PubMed 16330774.
2. ^ ^{a b c d} (Jun 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" (pdf). Reproduction. 123 (6). Retrieved on 2006-07-11.
3. ^ Rossi, MR, Ionov Y, Bakin AV, Cowell JK. (Dec 2005). "Truncating mutations in the ACVR2 gene attenuates activin signaling in prostate cancer cells". Cancer Genet Cytogenet. 163 (2): 123-9.. Entrez PubMed 16337854.
4. ^
5. ^ (Dec 2003) "Loss of heterozygosity and mutational analyses of the ACTRII gene locus in human colorectal tumors". Lab Invest. 83 ((12):). Entrez PubMed 14691305.