This gene encodes activin A type II receptor. Activins are dimeric growth and differentiation factors which belong to the transforming growth factor-beta (TGF-beta) superfamily of structurally related signaling proteins. Activins signal through a heteromeric complex of receptor serine kinases which include at least two type I (I and IB) and two type II (II and IIB) receptors. These receptors are all transmembrane proteins, composed of a ligand-binding extracellular domain with cysteine-rich region, a transmembrane domain, and a cytoplasmic domain with predicted serine/threonine specificity. Type I receptors are essential for signaling; and type II receptors are required for binding ligands and for expression of type I receptors. Type I and II receptors form a stable complex after ligand binding, resulting in phosphorylation of type I receptors by type II receptors. Type II receptors are considered to be constitutively active kinases.[3]
^Donaldson CJ, Mathews LS, Vale WW (May 1992). "Molecular cloning and binding properties of the human type II activin receptor". Biochem. Biophys. Res. Commun.184 (1): 310–6. doi:10.1016/0006-291X(92)91194-U. PMID1314589.
^Bondestam J, Horelli-Kuitunen N, Hildén K, Ritvos O, Aaltonen J (April 2000). "Assignment of ACVR2 and ACVR2B the human activin receptor type II and IIB genes to chromosome bands 2q22.2-->q23.3 and 3p22 and the human follistatin gene (FST) to chromosome 5q11.2 by FISH". Cytogenet. Cell Genet.87 (3-4): 219–20. doi:10.1159/000015429. PMID10702675.Check date values in: |year= / |date= mismatch (help)
^Lebrun JJ, Takabe K, Chen Y, Vale W (January 1999). "Roles of pathway-specific and inhibitory Smads in activin receptor signaling". Mol. Endocrinol.13 (1): 15–23. doi:10.1210/mend.13.1.0218. PMID9892009.
^De Winter JP, De Vries CJ, Van Achterberg TA, Ameerun RF, Feijen A, Sugino H et al. (May 1996). "Truncated activin type II receptors inhibit bioactivity by the formation of heteromeric complexes with activin type I. receptors". Exp. Cell Res.224 (2): 323–34. doi:10.1006/excr.1996.0142. PMID8612709.
^Lewis KA, Gray PC, Blount AL, MacConell LA, Wiater E, Bilezikjian LM et al. (March 2000). "Betaglycan binds inhibin and can mediate functional antagonism of activin signalling". Nature404 (6776): 411–4. doi:10.1038/35006129. PMID10746731.
^Martens JW, de Winter JP, Timmerman MA, McLuskey A, van Schaik RH, Themmen AP et al. (July 1997). "Inhibin interferes with activin signaling at the level of the activin receptor complex in Chinese hamster ovary cells". Endocrinology138 (7): 2928–36. doi:10.1210/endo.138.7.5250. PMID9202237.
^Tsuchida K, Nakatani M, Matsuzaki T, Yamakawa N, Liu Z, Bao Y et al. (October 2004). "Novel factors in regulation of activin signaling". Mol. Cell. Endocrinol.225 (1-2): 1–8. doi:10.1016/j.mce.2004.02.006. PMID15451561.
^Matsuzaki T, Hanai S, Kishi H, Liu Z, Bao Y, Kikuchi A et al. (May 2002). "Regulation of endocytosis of activin type II receptors by a novel PDZ protein through Ral/Ral-binding protein 1-dependent pathway". J. Biol. Chem.277 (21): 19008–18. doi:10.1074/jbc.M112472200. PMID11882656.
Further reading
Welt CK (2002). "The physiology and pathophysiology of inhibin, activin and follistatin in female reproduction". Curr. Opin. Obstet. Gynecol.14 (3): 317–23. doi:10.1097/00001703-200206000-00012. PMID12032389.
Matzuk MM, Bradley A (1992). "Cloning of the human activin receptor cDNA reveals high evolutionary conservation". Biochim. Biophys. Acta1130 (1): 105–8. doi:10.1016/0167-4781(92)90472-C. PMID1311955.
Mathews LS, Vale WW (1991). "Expression cloning of an activin receptor, a predicted transmembrane serine kinase". Cell65 (6): 973–82. doi:10.1016/0092-8674(91)90549-E. PMID1646080.
Xu J, McKeehan K, Matsuzaki K, McKeehan WL (1995). "Inhibin antagonizes inhibition of liver cell growth by activin by a dominant-negative mechanism". J. Biol. Chem.270 (11): 6308–13. doi:10.1074/jbc.270.11.6308. PMID7890768.
Attisano L, Cárcamo J, Ventura F, Weis FM, Massagué J, Wrana JL (1993). "Identification of human activin and TGF beta type I receptors that form heteromeric kinase complexes with type II receptors". Cell75 (4): 671–80. doi:10.1016/0092-8674(93)90488-C. PMID8242742.
Peng C, Huang TH, Jeung EB, Donaldson CJ, Vale WW, Leung PC (1993). "Expression of the type II activin receptor gene in the human placenta". Endocrinology133 (6): 3046–9. doi:10.1210/en.133.6.3046. PMID8243335.
De Winter JP, De Vries CJ, Van Achterberg TA, Ameerun RF, Feijen A, Sugino H et al. (1996). "Truncated activin type II receptors inhibit bioactivity by the formation of heteromeric complexes with activin type I. receptors". Exp. Cell Res.224 (2): 323–34. doi:10.1006/excr.1996.0142. PMID8612709.
Liu QY, Niranjan B, Gomes P, Gomm JJ, Davies D, Coombes RC et al. (1996). "Inhibitory effects of activin on the growth and morpholgenesis of primary and transformed mammary epithelial cells". Cancer Res.56 (5): 1155–63. PMID8640777.
Nishitoh H, Ichijo H, Kimura M, Matsumoto T, Makishima F, Yamaguchi A et al. (1996). "Identification of type I and type II serine/threonine kinase receptors for growth/differentiation factor-5". J. Biol. Chem.271 (35): 21345–52. doi:10.1074/jbc.271.35.21345. PMID8702914.
Macías-Silva M, Hoodless PA, Tang SJ, Buchwald M, Wrana JL (1998). "Specific activation of Smad1 signaling pathways by the BMP7 type I receptor, ALK2". J. Biol. Chem.273 (40): 25628–36. doi:10.1074/jbc.273.40.25628. PMID9748228.
Barbara NP, Wrana JL, Letarte M (1999). "Endoglin is an accessory protein that interacts with the signaling receptor complex of multiple members of the transforming growth factor-beta superfamily". J. Biol. Chem.274 (2): 584–94. doi:10.1074/jbc.274.2.584. PMID9872992.
Lux A, Attisano L, Marchuk DA (1999). "Assignment of transforming growth factor beta1 and beta3 and a third new ligand to the type I receptor ALK-1". J. Biol. Chem.274 (15): 9984–92. doi:10.1074/jbc.274.15.9984. PMID10187774.
D'Abronzo FH, Swearingen B, Klibanski A, Alexander JM (1999). "Mutational analysis of activin/transforming growth factor-beta type I and type II receptor kinases in human pituitary tumors". J. Clin. Endocrinol. Metab.84 (5): 1716–21. doi:10.1210/jc.84.5.1716. PMID10323406.
Ebisawa T, Tada K, Kitajima I, Tojo K, Sampath TK, Kawabata M et al. (1999). "Characterization of bone morphogenetic protein-6 signaling pathways in osteoblast differentiation". J. Cell. Sci. 112 ( Pt 20) (20): 3519–27. PMID10504300.
Shoji H, Tsuchida K, Kishi H, Yamakawa N, Matsuzaki T, Liu Z et al. (2000). "Identification and characterization of a PDZ protein that interacts with activin type II receptors". J. Biol. Chem.275 (8): 5485–92. doi:10.1074/jbc.275.8.5485. PMID10681527.
PDB gallery
1bte: CRYSTAL STRUCTURE OF THE EXTRACELLULAR DOMAIN OF THE TYPE II ACTIVIN RECEPTOR
1lx5: Crystal Structure of the BMP7/ActRII Extracellular Domain Complex
2goo: Ternary Complex of BMP-2 bound to BMPR-Ia-ECD and ActRII-ECD