Gene Symbol: Acvr1b
Description: activin A receptor, type 1B
Alias: 6820432J04, ALK-4, ActR-IB, ActRIB, Acvrlk4, Alk4, SKR2, activin receptor type-1B, activin receptor type IB, activin receptor-like kinase 4, serine/threonine-protein kinase receptor R2
Species: mouse
Products:     Acvr1b

Top Publications

  1. Hoodless P, Pye M, Chazaud C, Labbe E, Attisano L, Rossant J, et al. FoxH1 (Fast) functions to specify the anterior primitive streak in the mouse. Genes Dev. 2001;15:1257-71 pubmed
    ..These results show that FoxH1 functions in an activin/nodal-Smad signaling pathway that acts upstream of Foxa2 and is required specifically for patterning the APS and node in the mouse. ..
  2. Carvalho R, Itoh F, Goumans M, Lebrin F, Kato M, Takahashi S, et al. Compensatory signalling induced in the yolk sac vasculature by deletion of TGFbeta receptors in mice. J Cell Sci. 2007;120:4269-77 pubmed
    ..and ALK5(-/-) embryonic stem cells undergoing vasculogenesis, and these processes could be blocked by an ALK4 (ACVR1B)/ALK5 inhibitor...
  3. Ripoche D, Gout J, Pommier R, Jaafar R, Zhang C, Bartholin L, et al. Generation of a conditional mouse model to target Acvr1b disruption in adult tissues. Genesis. 2013;51:120-7 pubmed publisher
    ..Conventional deletion of Alk4 gene (Acvr1b) results in early embryonic lethality prior gastrulation, which has precluded study of Alk4 functions in postnatal ..
  4. Seki T, Hong K, Oh S. Nonoverlapping expression patterns of ALK1 and ALK5 reveal distinct roles of each receptor in vascular development. Lab Invest. 2006;86:116-29 pubmed
    ..The Alk5(lacZ) mice will be a valuable resource in identifying the in vivo cellular targets of TGF-beta family signals mediated by Alk5, both during embryonic development as well as in diverse pathological conditions. ..
  5. Müller M, Zheng F, Werner S, Alzheimer C. Transgenic mice expressing dominant-negative activin receptor IB in forebrain neurons reveal novel functions of activin at glutamatergic synapses. J Biol Chem. 2006;281:29076-84 pubmed
    ..This is the first demonstration that activin receptor signaling is essential to optimize the performance of neuronal circuits in the mature brain under physiological conditions. ..
  6. Miles D, Wakeling S, Stringer J, Van Den Bergen J, Wilhelm D, Sinclair A, et al. Signaling through the TGF beta-activin receptors ALK4/5/7 regulates testis formation and male germ cell development. PLoS ONE. 2013;8:e54606 pubmed publisher
    ..Inhibition of signaling through the receptors ALK4, ALK5 and ALK7, and ALK5 alone, demonstrated that TGF? signaling is required for testis cord formation during the ..
  7. Simmons D, Cross J. Determinants of trophoblast lineage and cell subtype specification in the mouse placenta. Dev Biol. 2005;284:12-24 pubmed
    ..Here, we review recent insights into the molecular pathways regulating trophoblast lineage segregation, stem cell maintenance, and subtype differentiation. ..
  8. Colas A, McKeithan W, Cunningham T, Bushway P, Garmire L, Duester G, et al. Whole-genome microRNA screening identifies let-7 and mir-18 as regulators of germ layer formation during early embryogenesis. Genes Dev. 2012;26:2567-79 pubmed publisher
    ..of computationally predicted targets followed by mutational analyses revealed that let-7 and miR-18 down-regulate Acvr1b and Smad2, respectively, to attenuate Nodal responsiveness and bias blastomeres to ectoderm and mesoderm fates...
  9. Andersson O, Reissmann E, Ibanez C. Growth differentiation factor 11 signals through the transforming growth factor-beta receptor ALK5 to regionalize the anterior-posterior axis. EMBO Rep. 2006;7:831-7 pubmed
    ..Here, we show that GDF11 can interact with type I receptors ALK4, ALK5 and ALK7, but predominantly uses ALK4 and ALK5 to activate a Smad3-dependent reporter gene...

More Information


  1. Wang Q, Yu Y, Zhang P, Chen Y, Li C, Chen J, et al. The crucial role of activin A/ALK4 pathway in the pathogenesis of Ang-II-induced atrial fibrosis and vulnerability to atrial fibrillation. Basic Res Cardiol. 2017;112:47 pubmed publisher
    ..Recent studies have implicated both activin A and its specific downstream component activin receptor-like kinase 4 (ALK4) in stimulating fibrosis in non-cardiac organs...
  2. Esguerra C, Nelles L, Vermeire L, Ibrahimi A, Crawford A, Derua R, et al. Ttrap is an essential modulator of Smad3-dependent Nodal signaling during zebrafish gastrulation and left-right axis determination. Development. 2007;134:4381-93 pubmed
    ..Stimulation of Alk4/EGF-CFC receptor complexes by Nodal activates Smad2/3, leading to left-sided expression of target genes that ..
  3. Collart C, Remacle J, Barabino S, van Grunsven L, Nelles L, Schellens A, et al. Smicl is a novel Smad interacting protein and cleavage and polyadenylation specificity factor associated protein. Genes Cells. 2005;10:897-906 pubmed
  4. Licona P, Chimal Monroy J, Soldevila G. Inhibins are the major activin ligands expressed during early thymocyte development. Dev Dyn. 2006;235:1124-32 pubmed
    ..Our data showed that Alk4, ActRIIA, ActRIIB, and Smads 2, 3, and 4, are expressed in fetal thymus (E14 > E15 > E16) and in thymocytes ..
  5. Lonardo E, Hermann P, Mueller M, Huber S, Balic A, Miranda Lorenzo I, et al. Nodal/Activin signaling drives self-renewal and tumorigenicity of pancreatic cancer stem cells and provides a target for combined drug therapy. Cell Stem Cell. 2011;9:433-46 pubmed publisher
    ..Knockdown or pharmacological inhibition of the Nodal/Activin receptor Alk4/7 in cancer stem cells virtually abrogated their self-renewal capacity and in vivo tumorigenicity, and reversed the ..
  6. Zhang Y, Cleary M, Si Y, Liu G, Eto Y, Kritzik M, et al. Inhibition of activin signaling induces pancreatic epithelial cell expansion and diminishes terminal differentiation of pancreatic beta-cells. Diabetes. 2004;53:2024-33 pubmed
    ..Follistatin participates in this process by promoting expansion of precursor cells during pancreas growth. ..
  7. Nomura M, Morinaga H, Zhu H, Wang L, Hasuzawa N, Takayanagi R, et al. Activation of activin type IB receptor signals in pancreatic ? cells leads to defective insulin secretion through the attenuation of ATP-sensitive K+ channel activity. Biochem Biophys Res Commun. 2014;450:440-6 pubmed publisher pancreatic ? cells, the Cre-loxP system was used to activate signaling through activin type IB receptor (ActRIB) in pancreatic ? cells...
  8. Oki S, Hashimoto R, Okui Y, Shen M, Mekada E, Otani H, et al. Sulfated glycosaminoglycans are necessary for Nodal signal transmission from the node to the left lateral plate in the mouse embryo. Development. 2007;134:3893-904 pubmed
    ..Inhibition of sulfated GAG biosynthesis prevents Nodal expression in the LPM. These data suggest that Nodal produced at the node might travel directly to the LPM via interaction with sulfated GAGs. ..
  9. Liang G, Zhang X, Wang J, Sun Y, Sun X, Cheng S, et al. Activin A accelerates the progression of fetal oocytes throughout meiosis and early oogenesis in the mouse. Stem Cells Dev. 2015;24:2455-65 pubmed publisher
    ..In this study, we reported that activin receptors (including ActRIA, ActRIB, ActRIIA, and ActRIIB) are expressed throughout the development of the mouse ovaries from 12...
  10. Jörnvall H, Reissmann E, Andersson O, Mehrkash M, Ibanez C. ALK7, a receptor for nodal, is dispensable for embryogenesis and left-right patterning in the mouse. Mol Cell Biol. 2004;24:9383-9 pubmed
    ..Two type I serine/threonine kinase receptors have been identified for Nodal, ALK4 and ALK7...
  11. Nakamura M, Matzuk M, Gerstmayer B, Bosio A, Lauster R, Miyachi Y, et al. Control of pelage hair follicle development and cycling by complex interactions between follistatin and activin. FASEB J. 2003;17:497-9 pubmed
    ..These observations suggest that follistatin and activin interaction plays an important role in both HF development and cycling, possibly in part by regulating expression of BMP-2 and its antagonist. ..
  12. Gu Z, Nomura M, Simpson B, Lei H, Feijen A, van den Eijnden van Raaij J, et al. The type I activin receptor ActRIB is required for egg cylinder organization and gastrulation in the mouse. Genes Dev. 1998;12:844-57 pubmed
    b>ActRIB is a type I transmembrane serine/threonine kinase receptor that has been shown to form heteromeric complexes with the type II activin receptors to mediate activin signal...
  13. Andersson O, Reissmann E, Jörnvall H, Ibanez C. Synergistic interaction between Gdf1 and Nodal during anterior axis development. Dev Biol. 2006;293:370-81 pubmed
    ..Receptor reconstitution experiments indicated that GDF-1, like Nodal, can signal through the type I receptors ALK4 and ALK7...
  14. Mishina Y, Crombie R, Bradley A, Behringer R. Multiple roles for activin-like kinase-2 signaling during mouse embryogenesis. Dev Biol. 1999;213:314-26 pubmed
  15. Verschueren K, Dewulf N, Goumans M, Lonnoy O, Feijen A, Grimsby S, et al. Expression of type I and type IB receptors for activin in midgestation mouse embryos suggests distinct functions in organogenesis. Mech Dev. 1995;52:109-23 pubmed
  16. Cai W, Guzzo R, Wei K, Willems E, Davidovics H, Mercola M. A Nodal-to-TGF? cascade exerts biphasic control over cardiopoiesis. Circ Res. 2012;111:876-81 pubmed publisher
    ..TGF?, however, becomes uniquely responsible for controlling subsequent lineage segregation by stimulating vascular smooth muscle and endothelial lineages and simultaneously blocking cardiomyocyte differentiation. ..
  17. Andersson O, Bertolino P, Ibanez C. Distinct and cooperative roles of mammalian Vg1 homologs GDF1 and GDF3 during early embryonic development. Dev Biol. 2007;311:500-11 pubmed
    ..In addition, and similar to GDF1, we find that GDF3 signaling can be mediated by the type I receptor ALK4, type II receptors ActRIIA and ActRIIB, and the co-receptor Cripto to activate Smad-dependent reporter genes...
  18. Renucci A, Lemarchandel V, Rosa F. An activated form of type I serine/threonine kinase receptor TARAM-A reveals a specific signalling pathway involved in fish head organiser formation. Development. 1996;122:3735-43 pubmed
    ..Our data suggest the existence in fish of a specific TGF-beta-related pathway for anterior dorsal mesoderm induction, possibly mediated by TARAM-A and activated at the late blastula stage by localized dorsal determinant. ..
  19. Mizuno Y, Tokuzawa Y, Ninomiya Y, Yagi K, Yatsuka Kanesaki Y, Suda T, et al. miR-210 promotes osteoblastic differentiation through inhibition of AcvR1b. FEBS Lett. 2009;583:2263-8 pubmed publisher
    ..A reporter assay demonstrated that the activin A receptor type 1B (AcvR1b) gene was a target for miR-210...
  20. Zhu J, Lin S, Zou C, Makanji Y, Jardetzky T, Woodruff T. Inhibin ?-subunit N terminus interacts with activin type IB receptor to disrupt activin signaling. J Biol Chem. 2012;287:8060-70 pubmed publisher
    ..We hypothesized that the ?-subunit N-terminal extension region interacts with the activin type I receptor (ALK4) to antagonize activin signaling in the pituitary...
  21. Natale D, Hemberger M, Hughes M, Cross J. Activin promotes differentiation of cultured mouse trophoblast stem cells towards a labyrinth cell fate. Dev Biol. 2009;335:120-31 pubmed publisher
    ..These results suggest that Activin rather than TGF-beta (or Nodal) acts directly on TS cells influencing both TS cell maintenance and cell fate, depending on whether the cells are also exposed to FGF4. ..
  22. Kemaladewi D, de Gorter D, Aartsma Rus A, van Ommen G, Ten Dijke P, t Hoen P, et al. Cell-type specific regulation of myostatin signaling. FASEB J. 2012;26:1462-72 pubmed publisher
    ..We therefore determined the contribution of myostatin type I receptors activin receptor-like kinase-4 (ALK4) and -5 (ALK5) and different coreceptors in C2C12 myoblasts, C3H10T1/2 mesenchymal stem cells, and 3T3-L1 ..
  23. Jeruss J, Santiago J, Woodruff T. Localization of activin and inhibin subunits, receptors and SMADs in the mouse mammary gland. Mol Cell Endocrinol. 2003;203:185-96 pubmed
    ..The expression of the activin receptors (ActRIIA, ActRIIB and ActRIB), the inhibin co-receptor (betaglycan), and ligand subunit (alpha, beta A and beta B), mRNA was measured by semi-..
  24. Chen Y, Wang Q, Li C, Hou J, Chen X, Zhou Q, et al. Haplodeficiency of activin receptor-like kinase 4 alleviates myocardial infarction-induced cardiac fibrosis and preserves cardiac function. J Mol Cell Cardiol. 2017;105:1-11 pubmed publisher
    ..Recent studies have implicated both activin and its specific downstream component ALK4 in stimulating fibrosis in non-cardiac organs...
  25. Schmitt J, Mielke R, Schrewe H. Genomic organization of a mouse type I activin receptor. Biochem Biophys Res Commun. 1995;213:211-7 pubmed
    ..Knowledge of the structure of the ActRIA gene is essential for the production of ActRIA deficient mice by homologous recombination. ..
  26. Yan G, Zhang L, Fang T, Zhang Q, Wu S, Jiang Y, et al. MicroRNA-145 suppresses mouse granulosa cell proliferation by targeting activin receptor IB. FEBS Lett. 2012;586:3263-70 pubmed publisher
    ..Altogether, this study revealed that miR-145 suppresses mGC proliferation by targeting ACVRIB. ..
  27. Spiller C, Feng C, Jackson A, Gillis A, Rolland A, Looijenga L, et al. Endogenous Nodal signaling regulates germ cell potency during mammalian testis development. Development. 2012;139:4123-32 pubmed publisher
    ..Thus, Nodal signaling provides a molecular control mechanism that regulates male germ cell potency in normal development and testicular cancer. ..
  28. Bamberger C, Schärer A, Antsiferova M, Tychsen B, Pankow S, Müller M, et al. Activin controls skin morphogenesis and wound repair predominantly via stromal cells and in a concentration-dependent manner via keratinocytes. Am J Pathol. 2005;167:733-47 pubmed
    ..These results demonstrate that activin affects both stromal cells and keratinocytes in normal and wounded skin and that the effect on keratinocytes is dose-dependent in vivo. ..
  29. Qiu W, Li X, Tang H, Huang A, Panteleyev A, Owens D, et al. Conditional activin receptor type 1B (Acvr1b) knockout mice reveal hair loss abnormality. J Invest Dermatol. 2011;131:1067-76 pubmed publisher
    The in vivo functions of the activin A receptor type 1b (Acvr1b) have been difficult to study because Acvr1b(-/-) mice die during embryogenesis...
  30. Gokoffski K, Wu H, Beites C, Kim J, Kim E, Matzuk M, et al. Activin and GDF11 collaborate in feedback control of neuroepithelial stem cell proliferation and fate. Development. 2011;138:4131-42 pubmed publisher
    ..Thus, our findings demonstrate a close connection between the signals involved in the control of tissue size and those that regulate the proportions of different cell types...
  31. Peng J, Fullerton P, Monsivais D, Clementi C, Su G, Matzuk M. Uterine Activin-Like Kinase 4 Regulates Trophoblast Development During Mouse Placentation. Mol Endocrinol. 2015;29:1684-93 pubmed publisher
    ..of Nodal signaling in the uterus, we established a mouse model to conditionally ablate activin-like kinase 4 (ALK4; the Nodal type 1 receptor) using Cre recombinase driven by the progesterone receptor promoter sequences (Pgr-Cre)...
  32. Li C, Chen Y, Wang Q, Hou J, Wang H, Wang Y, et al. Partial inhibition of activin receptor-like kinase 4 attenuates pressure overload-induced cardiac fibrosis and improves cardiac function. J Hypertens. 2016;34:1766-77 pubmed publisher
    Activin receptor-like kinase 4 (ALK4), a downstream receptor of transforming growth factor-β superfamily, is highly expressed in the mammal heart...