| 释义 |
- Function
- Interactions
- References
- External links
- Further reading
{{Infobox_gene}}Activin receptor type-1B is a protein that in humans is encoded by the ACVR1B gene.[1][2]ACVR1B or ALK-4 acts as a transducer of activin or activin-like ligands (e.g., inhibin) signals. Activin binds to either ACVR2A or ACVR2B and then forms a complex with ACVR1B. These go on to recruit the R-SMADs SMAD2 or SMAD3.[3] ACVR1B also transduces signals of nodal, GDF-1, and Vg1; however, unlike activin, they require other coreceptor molecules such as the protein Cripto.[4] Function 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 a 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. This gene encodes activin A type IB receptor, composed of 11 exons. Alternative splicing and alternative polyadenylation result in 3 fully described transcript variants. The mRNA expression of variants 1, 2, and 3 is confirmed, and a potential fourth variant contains an alternative exon 8 and lacks exons 9 through 11, but its mRNA expression has not been confirmed.[2] Interactions ACVR1B has been shown to interact with - ACVR2A,[6][5] and ACVR2B[6][7]
References 1. ^{{cite journal | vauthors = ten Dijke P, Ichijo H, Franzén P, Schulz P, Saras J, Toyoshima H, Heldin CH, Miyazono K | title = Activin receptor-like kinases: a novel subclass of cell-surface receptors with predicted serine/threonine kinase activity | journal = Oncogene | volume = 8 | issue = 10 | pages = 2879–87 | date = October 1993 | pmid = 8397373 | pmc = | doi = }}
2. ^1 {{cite web | title = Entrez Gene: ACVR1B activin A receptor, type IB| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=91| accessdate = }}
3. ^{{cite journal | vauthors = Inman GJ, Nicolás FJ, Callahan JF, Harling JD, Gaster LM, Reith AD, Laping NJ, Hill CS | title = SB-431542 is a potent and specific inhibitor of transforming growth factor-beta superfamily type I activin receptor-like kinase (ALK) receptors ALK4, ALK5, and ALK7 | journal = Mol. Pharmacol. | volume = 62 | issue = 1 | pages = 65–74 | year = 2002 | pmid = 12065756 | doi = 10.1124/mol.62.1.65 }}
4. ^{{cite journal | vauthors = Harrison CA, Gray PC, Koerber SC, Fischer W, Vale W | title = Identification of a functional binding site for activin on the type I receptor ALK4 | journal = J. Biol. Chem. | volume = 278 | issue = 23 | pages = 21129–35 | year = 2003 | pmid = 12665502 | doi = 10.1074/jbc.M302015200 }}
5. ^{{cite journal | vauthors = Lebrun JJ, Takabe K, Chen Y, Vale W | title = Roles of pathway-specific and inhibitory Smads in activin receptor signaling | journal = Mol. Endocrinol. | volume = 13 | issue = 1 | pages = 15–23 | date = January 1999 | pmid = 9892009 | doi = 10.1210/mend.13.1.0218 }}
6. ^{{cite journal | vauthors = Attisano L, Wrana JL, Montalvo E, Massagué J | title = Activation of signalling by the activin receptor complex | journal = Mol. Cell. Biol. | volume = 16 | issue = 3 | pages = 1066–73 | date = March 1996 | pmid = 8622651 | pmc = 231089 | doi = 10.1128/MCB.16.3.1066}}
7. ^1 {{cite journal | vauthors = De Winter JP, De Vries CJ, Van Achterberg TA, Ameerun RF, Feijen A, Sugino H, De Waele P, Huylebroeck D, Verschueren K, Van Den Eijden-Van Raaij AJ | title = Truncated activin type II receptors inhibit bioactivity by the formation of heteromeric complexes with activin type I. receptors | journal = Exp. Cell Res. | volume = 224 | issue = 2 | pages = 323–34 | date = May 1996 | pmid = 8612709 | doi = 10.1006/excr.1996.0142 }}
External links- {{UCSC gene info|ACVR1B}}
Further reading {{refbegin | 2}}- {{cite journal | vauthors = Welt CK | title = The physiology and pathophysiology of inhibin, activin and follistatin in female reproduction | journal = Curr. Opin. Obstet. Gynecol. | volume = 14 | issue = 3 | pages = 317–23 | year = 2002 | pmid = 12032389 | doi = 10.1097/00001703-200206000-00012 }}
- {{cite journal | vauthors = Liu F, Ventura F, Doody J, Massagué J | title = Human type II receptor for bone morphogenic proteins (BMPs): extension of the two-kinase receptor model to the BMPs | journal = Mol. Cell. Biol. | volume = 15 | issue = 7 | pages = 3479–86 | year = 1995 | pmid = 7791754 | pmc = 230584 | doi = 10.1128/mcb.15.7.3479}}
- {{cite journal | vauthors = Xu J, Matsuzaki K, McKeehan K, Wang F, Kan M, McKeehan WL | title = Genomic structure and cloned cDNAs predict that four variants in the kinase domain of serine/threonine kinase receptors arise by alternative splicing and poly(A) addition | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 91 | issue = 17 | pages = 7957–61 | year = 1994 | pmid = 8058741 | pmc = 44523 | doi = 10.1073/pnas.91.17.7957 }}
- {{cite journal | vauthors = Cárcamo J, Weis FM, Ventura F, Wieser R, Wrana JL, Attisano L, Massagué J | title = Type I receptors specify growth-inhibitory and transcriptional responses to transforming growth factor beta and activin | journal = Mol. Cell. Biol. | volume = 14 | issue = 6 | pages = 3810–21 | year = 1994 | pmid = 8196624 | pmc = 358748 | doi = 10.1128/MCB.14.6.3810}}
- {{cite journal | vauthors = De Winter JP, De Vries CJ, Van Achterberg TA, Ameerun RF, Feijen A, Sugino H, De Waele P, Huylebroeck D, Verschueren K, Van Den Eijden-Van Raaij AJ | title = Truncated activin type II receptors inhibit bioactivity by the formation of heteromeric complexes with activin type I. receptors | journal = Exp. Cell Res. | volume = 224 | issue = 2 | pages = 323–34 | year = 1996 | pmid = 8612709 | doi = 10.1006/excr.1996.0142 }}
- {{cite journal | vauthors = Attisano L, Wrana JL, Montalvo E, Massagué J | title = Activation of signalling by the activin receptor complex | journal = Mol. Cell. Biol. | volume = 16 | issue = 3 | pages = 1066–73 | year = 1996 | pmid = 8622651 | pmc = 231089 | doi = 10.1128/MCB.16.3.1066}}
- {{cite journal | vauthors = Lebrun JJ, Vale WW | title = Activin and inhibin have antagonistic effects on ligand-dependent heteromerization of the type I and type II activin receptors and human erythroid differentiation | journal = Mol. Cell. Biol. | volume = 17 | issue = 3 | pages = 1682–91 | year = 1997 | pmid = 9032295 | pmc = 231893 | doi = 10.1128/MCB.17.3.1682}}
- {{cite journal | vauthors = Röijer E, Miyazono K, Aström AK, Geurts van Kessel A, ten Dijke P, Stenman G | title = Chromosomal localization of three human genes encoding members of the TGF-beta superfamily of type I serine/threonine kinase receptors | journal = Mamm. Genome | volume = 9 | issue = 3 | pages = 266–8 | year = 1998 | pmid = 9501322 | doi = 10.1007/s003359900745 }}
- {{cite journal | vauthors = Souchelnytskyi S, Nakayama T, Nakao A, Morén A, Heldin CH, Christian JL, ten Dijke P | title = Physical and functional interaction of murine and Xenopus Smad7 with bone morphogenetic protein receptors and transforming growth factor-beta receptors | journal = J. Biol. Chem. | volume = 273 | issue = 39 | pages = 25364–70 | year = 1998 | pmid = 9738003 | doi = 10.1074/jbc.273.39.25364 }}
- {{cite journal | vauthors = Hashimoto O, Yamato K, Koseki T, Ohguchi M, Ishisaki A, Shoji H, Nakamura T, Hayashi Y, Sugino H, Nishihara T | title = The role of activin type I receptors in activin A-induced growth arrest and apoptosis in mouse B-cell hybridoma cells | journal = Cell. Signal. | volume = 10 | issue = 10 | pages = 743–9 | year = 1998 | pmid = 9884026 | doi = 10.1016/S0898-6568(98)00021-7 }}
- {{cite journal | vauthors = Lebrun JJ, Takabe K, Chen Y, Vale W | title = Roles of pathway-specific and inhibitory Smads in activin receptor signaling | journal = Mol. Endocrinol. | volume = 13 | issue = 1 | pages = 15–23 | year = 1999 | pmid = 9892009 | doi = 10.1210/mend.13.1.0218 }}
- {{cite journal | vauthors = Gray PC, Greenwald J, Blount AL, Kunitake KS, Donaldson CJ, Choe S, Vale W | title = Identification of a binding site on the type II activin receptor for activin and inhibin | journal = J. Biol. Chem. | volume = 275 | issue = 5 | pages = 3206–12 | year = 2000 | pmid = 10652306 | doi = 10.1074/jbc.275.5.3206 }}
- {{cite journal | vauthors = Zhou Y, Sun H, Danila DC, Johnson SR, Sigai DP, Zhang X, Klibanski A | title = Truncated activin type I receptor Alk4 isoforms are dominant negative receptors inhibiting activin signaling | journal = Mol. Endocrinol. | volume = 14 | issue = 12 | pages = 2066–75 | year = 2000 | pmid = 11117535 | doi = 10.1210/me.14.12.2066 }}
- {{cite journal | vauthors = Su GH, Bansal R, Murphy KM, Montgomery E, Yeo CJ, Hruban RH, Kern SE | title = ACVR1B (ALK4, activin receptor type 1B) gene mutations in pancreatic carcinoma | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 98 | issue = 6 | pages = 3254–7 | year = 2001 | pmid = 11248065 | pmc = 30640 | doi = 10.1073/pnas.051484398 }}
- {{cite journal | vauthors = Chapman SC, Woodruff TK | title = Modulation of activin signal transduction by inhibin B and inhibin-binding protein (INhBP) | journal = Mol. Endocrinol. | volume = 15 | issue = 4 | pages = 668–79 | year = 2001 | pmid = 11266516 | doi = 10.1210/me.15.4.668 }}
- {{cite journal | vauthors = Wurthner JU, Frank DB, Felici A, Green HM, Cao Z, Schneider MD, McNally JG, Lechleider RJ, Roberts AB | title = Transforming growth factor-beta receptor-associated protein 1 is a Smad4 chaperone | journal = J. Biol. Chem. | volume = 276 | issue = 22 | pages = 19495–502 | year = 2001 | pmid = 11278302 | doi = 10.1074/jbc.M006473200 }}
- {{cite journal | vauthors = Parks WT, Frank DB, Huff C, Renfrew Haft C, Martin J, Meng X, de Caestecker MP, McNally JG, Reddi A, Taylor SI, Roberts AB, Wang T, Lechleider RJ | title = Sorting nexin 6, a novel SNX, interacts with the transforming growth factor-beta family of receptor serine-threonine kinases | journal = J. Biol. Chem. | volume = 276 | issue = 22 | pages = 19332–9 | year = 2001 | pmid = 11279102 | doi = 10.1074/jbc.M100606200 }}
- {{cite journal | vauthors = Birkey Reffey S, Wurthner JU, Parks WT, Roberts AB, Duckett CS | title = X-linked inhibitor of apoptosis protein functions as a cofactor in transforming growth factor-beta signaling | journal = J. Biol. Chem. | volume = 276 | issue = 28 | pages = 26542–9 | year = 2001 | pmid = 11356828 | doi = 10.1074/jbc.M100331200 }}
- {{cite journal | vauthors = Bianco C, Adkins HB, Wechselberger C, Seno M, Normanno N, De Luca A, Sun Y, Khan N, Kenney N, Ebert A, Williams KP, Sanicola M, Salomon DS | title = Cripto-1 activates nodal- and ALK4-dependent and -independent signaling pathways in mammary epithelial Cells | journal = Mol. Cell. Biol. | volume = 22 | issue = 8 | pages = 2586–97 | year = 2002 | pmid = 11909953 | pmc = 133714 | doi = 10.1128/MCB.22.8.2586-2597.2002 }}
{{refend}}{{PDB Gallery|geneid=91}}{{TGF beta signaling}}{{Serine/threonine-specific protein kinases}}{{Enzymes}}{{TGFβ receptor superfamily modulators}}{{Portal bar|Molecular and Cellular Biology|border=no}}{{DEFAULTSORT:Acvr1b}} 5 : GS domain|TS domain|S/T domain|Human proteins|EC 2.7.11 |