| Written | 2007-06 | Sarah Boles, Eddy Chau, Barbara Jung |
| | GI fellowship program Division of Gastroenterology, University of California, San Diego 9500 Gilman Drive 0063 La Jolla, CA, 92093-0063, USA |
| Updated | 2012-05 | Jessica Bauer, Sarah Boles, Eddy Chau, Barbara Jung |
| | Department of Medicine, Division of Gastroenterology, Northwestern University, Chicago 303 East Superior Street, IL, 60611, USA (JB, BJ); Division of Gastroenterology, University of California, San Diego 9500 Gilman Drive 0063 La Jolla, CA, 92093-0063, USA (SB, EC) |
| Description | ACVR2 is a member of the transforming growth factor beta (TGF-β) receptor family. It is a 70-75kDa protein consisting of 513 amino acids. It is a transmembrane receptor for activin, with a cysteine-rich extracellular ligand-binding domain, a single pass transmembrane domain, and an intracellular domain with constitutive serine/threonine kinase activity.
Upon binding activin, ACVR2 associates with and phosphorylates ACVR1.
ACVR1, in turn, phosphorylates Smad2 and/or Smad3. Phosphorylated Smad2 and Smad3 associate with Smad4, translocate to the nucleus, and regulate gene expression.
There may be other non-Smad pathways in activin signal transduction. These include the RhoA-ROCK-MEKK1-JNK and MEKK1-p38 pathways.
In addition to activin, other ligands such as myostatin, nodal, and bone morphogenetic protein 7 (BMP-7) may also bind to ACVR2 and affect signal transduction. |
| Expression | Abundant expression in multiple tissues, including skeletal muscle, stomach, heart, endometrium, testes, prostate, ovary, and neural tissues. The cell surface level of ACVR2 and ACVR2B is regulated by proteins called ARIPs (activin receptor-interacting proteins). |
| Localisation | Cell surface, spanning cytoplasmic membrane. |
| Function | Activin signals via its receptors, ACVR1 and ACVR2, and has roles in cell proliferation, differentiation, apoptosis, metabolism, immune response, wound repair, and endocrine function. |
| Activation of signalling by the activin receptor complex. |
| Attisano L, Wrana JL, Montalvo E, Massague J. |
| Mol Cell Biol. 1996 Mar;16(3):1066-73. |
| PMID 8622651 |
| |
| Activin signaling and its role in regulation of cell proliferation, apoptosis, and carcinogenesis. |
| Chen YG, Wang Q, Lin SL, Chang CD, Chuang J, Ying SY. |
| Exp Biol Med (Maywood). 2006 May;231(5):534-44. (REVIEW) |
| PMID 16636301 |
| |
| Flanking nucleotide specificity for DNA mismatch repair-deficient frameshifts within activin receptor 2 (ACVR2). |
| Chung H, Chaudhry J, Lai JF, Young DJ, Carethers JM. |
| Mutat Res. 2012 Jan 3;729(1-2):73-80. doi: 10.1016/j.mrfmmm.2011.09.009. Epub 2011 Oct 5. |
| PMID 22001236 |
| |
| Genetic association of the activin A receptor gene (ACVR2A) and pre-eclampsia. |
| Fitzpatrick E, Johnson MP, Dyer TD, Forrest S, Elliott K, Blangero J, Brennecke SP, Moses EK. |
| Mol Hum Reprod. 2009 Mar;15(3):195-204. Epub 2009 Jan 6. |
| PMID 19126782 |
| |
| Expression of type II activin receptor genes during differentiation of human K562 cells and cDNA cloning of the human type IIB activin receptor. |
| Hilden K, Tuuri T, Eramaa M, Ritvos O. |
| Blood. 1994 Apr 15;83(8):2163-70. |
| PMID 8161782 |
| |
| Loss of activin receptor type 2 protein expression in microsatellite unstable colon cancers. |
| Jung B, Doctolero RT, Tajima A, Nguyen AK, Keku T, Sandler RS, Carethers JM. |
| Gastroenterology. 2004 Mar;126(3):654-9. |
| PMID 14988818 |
| |
| Activin signaling in microsatellite stable colon cancers is disrupted by a combination of genetic and epigenetic mechanisms. |
| Jung B, Gomez J, Chau E, Cabral J, Lee JK, Anselm A, Slowik P, Ream-Robinson D, Messer K, Sporn J, Shin SK, Boland CR, Goel A, Carethers JM. |
| PLoS One. 2009 Dec 14;4(12):e8308. |
| PMID 20011542 |
| |
| Influence of target gene mutations on survival, stage and histology in sporadic microsatellite unstable colon cancers. |
| Jung B, Smith EJ, Doctolero RT, Gervaz P, Alonso JC, Miyai K, Keku T, Sandler RS, Carethers JM. |
| Int J Cancer. 2006 May 15;118(10):2509-13. |
| PMID 16380996 |
| |
| Activin type 2 receptor restoration in MSI-H colon cancer suppresses growth and enhances migration with activin. |
| Jung BH, Beck SE, Cabral J, Chau E, Cabrera BL, Fiorino A, Smith EJ, Bocanegra M, Carethers JM. |
| Gastroenterology. 2007 Feb;132(2):633-44. Epub 2006 Nov 16. |
| PMID 17258738 |
| |
| Characterization of isoforms of activin receptor-interacting protein 2 that augment activin signaling. |
| Liu ZH, Tsuchida K, Matsuzaki T, Bao YL, Kurisaki A, Sugino H. |
| J Endocrinol. 2006 May;189(2):409-21. |
| PMID 16648306 |
| |
| Characterization of type II activin receptors. Binding, processing, and phosphorylation. |
| Mathews LS, Vale WW. |
| J Biol Chem. 1993 Sep 5;268(25):19013-8. |
| PMID 8395525 |
| |
