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Gene Review

Acvrl1  -  activin A receptor, type II-like 1

Mus musculus

Synonyms: AI115505, AI427544, ALK-1, Activin receptor-like kinase 1, Acvrlk1, ...
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Disease relevance of Acvrl1


High impact information on Acvrl1


Chemical compound and disease context of Acvrl1


Biological context of Acvrl1

  • An Acvrl1(+/-) mouse with profound liver involvement also displayed a secondary cardiac phenotype, similar to that observed in human patients [10].
  • In contrast to Alk1 mutants, endoglin mutants do not show profound vessel dilation or downregulation of arterial ephrinB2 [11].
  • Isolation of a regulatory region of activin receptor-like kinase 1 gene sufficient for arterial endothelium-specific expression [12].
  • We created a novel null mutant mouse line for Alk1 (Alk1lacZ) by replacing its exons, including the one that encodes the transmembrane domain, with the beta-galactosidase gene [13].
  • Alk1 expression is greatly diminished in adult arteries, but is induced in preexisting feeding arteries and newly forming arterial vessels during wound healing and tumor angiogenesis [13].

Anatomical context of Acvrl1

  • Our results indicate a pivotal role for endoglin in the balance of ALK1 and ALK5 signalling to regulate endothelial cell proliferation [7].
  • Using Alk1lacZ mice, we show that Alk1 is predominantly expressed in developing arterial endothelium [13].
  • Contrary to the current view of HHT as venous disease, our findings suggest that the arterioles rather than the venules are the primary vessels affected by the loss of an Alk1 allele, and that blood vessels with reduction in Alk1 expression may harbor defects in responding to demands for vascular remodeling [13].
  • An activin receptor-like kinase (ALK) 4/5/7 inhibitor, SB431542, also antagonised both oocyte and GDF9 bioactivity in a dose-dependent manner [14].
  • In this study, we have analyzed the temporal and spatial expression pattern of ALK-1 mRNA in mouse embryos from the one-cell zygote until 12.5 dpc using RT-PCR and in situ hybridization [15].

Associations of Acvrl1 with chemical compounds

  • We have previously identified a series of type I serine/threonine kinase receptors, termed activin receptor-like kinase (ALK)-1 to -6 [16].
  • Expression of ALK-1, a type 1 serine/threonine kinase receptor, coincides with sites of vasculogenesis and angiogenesis in early mouse development [15].
  • This genetic abnormality leads to the expression of the NPM-ALK fusion protein, which encodes a constitutively active tyrosine kinase that plays a causative role in lymphomagenesis [4].

Physical interactions of Acvrl1


Regulatory relationships of Acvrl1


Other interactions of Acvrl1


Analytical, diagnostic and therapeutic context of Acvrl1

  • The similarity of affected organs, age-dependent penetrance, histological similarity of the lesions and recapitulation of a secondary phenotype suggest that the Acvrl1(+/-) mice are an appropriate animal model for the identification of additional genetic and environmental factors that cause pathology in HHT type 2 patients [10].
  • To define the function of ALK1 during development, we inactivated the ALK1 gene in mice by gene targeting [1].
  • On Western blots, a goat polyclonal antibody detected the native ALK-1 protein in bone marrow stromal cells, lung, brain, kidney and spleen [20].


  1. Activin receptor-like kinase 1 modulates transforming growth factor-beta 1 signaling in the regulation of angiogenesis. Oh, S.P., Seki, T., Goss, K.A., Imamura, T., Yi, Y., Donahoe, P.K., Li, L., Miyazono, K., ten Dijke, P., Kim, S., Li, E. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  2. Arteriovenous malformations in mice lacking activin receptor-like kinase-1. Urness, L.D., Sorensen, L.K., Li, D.Y. Nat. Genet. (2000) [Pubmed]
  3. Regulation of ALK-1 signaling by the nuclear receptor LXRbeta. Mo, J., Fang, S.J., Chen, W., Blobe, G.C. J. Biol. Chem. (2002) [Pubmed]
  4. The oncogenic fusion protein nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) induces two distinct malignant phenotypes in a murine retroviral transplantation model. Miething, C., Grundler, R., Fend, F., Hoepfl, J., Mugler, C., von Schilling, C., Morris, S.W., Peschel, C., Duyster, J. Oncogene (2003) [Pubmed]
  5. Domain-specific function of ShcC docking protein in neuroblastoma cells. Miyake, I., Hakomori, Y., Misu, Y., Nakadate, H., Matsuura, N., Sakamoto, M., Sakai, R. Oncogene (2005) [Pubmed]
  6. ALK5- and TGFBR2-independent role of ALK1 in the pathogenesis of hereditary hemorrhagic telangiectasia type 2. Park, S.O., Lee, Y.J., Seki, T., Hong, K.H., Fliess, N., Jiang, Z., Park, A., Wu, X., Kaartinen, V., Roman, B.L., Oh, S.P. Blood (2008) [Pubmed]
  7. Endoglin promotes endothelial cell proliferation and TGF-beta/ALK1 signal transduction. Lebrin, F., Goumans, M.J., Jonker, L., Carvalho, R.L., Valdimarsdottir, G., Thorikay, M., Mummery, C., Arthur, H.M., ten Dijke, P. EMBO J. (2004) [Pubmed]
  8. Functional analysis of mutations in the kinase domain of the TGF-beta receptor ALK1 reveals different mechanisms for induction of hereditary hemorrhagic telangiectasia. Gu, Y., Jin, P., Zhang, L., Zhao, X., Gao, X., Ning, Y., Meng, A., Chen, Y.G. Blood (2006) [Pubmed]
  9. Characterization of the expression of the ALK receptor tyrosine kinase in mice. Vernersson, E., Khoo, N.K., Henriksson, M.L., Roos, G., Palmer, R.H., Hallberg, B. Gene Expr. Patterns (2006) [Pubmed]
  10. A mouse model for hereditary hemorrhagic telangiectasia (HHT) type 2. Srinivasan, S., Hanes, M.A., Dickens, T., Porteous, M.E., Oh, S.P., Hale, L.P., Marchuk, D.A. Hum. Mol. Genet. (2003) [Pubmed]
  11. Loss of distinct arterial and venous boundaries in mice lacking endoglin, a vascular-specific TGFbeta coreceptor. Sorensen, L.K., Brooke, B.S., Li, D.Y., Urness, L.D. Dev. Biol. (2003) [Pubmed]
  12. Isolation of a regulatory region of activin receptor-like kinase 1 gene sufficient for arterial endothelium-specific expression. Seki, T., Hong, K.H., Yun, J., Kim, S.J., Oh, S.P. Circ. Res. (2004) [Pubmed]
  13. Arterial endothelium-specific activin receptor-like kinase 1 expression suggests its role in arterialization and vascular remodeling. Seki, T., Yun, J., Oh, S.P. Circ. Res. (2003) [Pubmed]
  14. Molecular basis of oocyte-paracrine signalling that promotes granulosa cell proliferation. Gilchrist, R.B., Ritter, L.J., Myllymaa, S., Kaivo-Oja, N., Dragovic, R.A., Hickey, T.E., Ritvos, O., Mottershead, D.G. J. Cell. Sci. (2006) [Pubmed]
  15. Expression of ALK-1, a type 1 serine/threonine kinase receptor, coincides with sites of vasculogenesis and angiogenesis in early mouse development. Roelen, B.A., van Rooijen, M.A., Mummery, C.L. Dev. Dyn. (1997) [Pubmed]
  16. Identification of type I receptors for osteogenic protein-1 and bone morphogenetic protein-4. ten Dijke, P., Yamashita, H., Sampath, T.K., Reddi, A.H., Estevez, M., Riddle, D.L., Ichijo, H., Heldin, C.H., Miyazono, K. J. Biol. Chem. (1994) [Pubmed]
  17. Smad7 and protein phosphatase 1alpha are critical determinants in the duration of TGF-beta/ALK1 signaling in endothelial cells. Valdimarsdottir, G., Goumans, M.J., Itoh, F., Itoh, S., Heldin, C.H., ten Dijke, P. BMC Cell Biol. (2006) [Pubmed]
  18. Endoglin null endothelial cells proliferate faster and are more responsive to transforming growth factor beta1 with higher affinity receptors and an activated Alk1 pathway. Pece-Barbara, N., Vera, S., Kathirkamathamby, K., Liebner, S., Di Guglielmo, G.M., Dejana, E., Wrana, J.L., Letarte, M. J. Biol. Chem. (2005) [Pubmed]
  19. Nonoverlapping expression patterns of ALK1 and ALK5 reveal distinct roles of each receptor in vascular development. Seki, T., Hong, K.H., Oh, S.P. Lab. Invest. (2006) [Pubmed]
  20. Cloning and characterization of the murine activin receptor like kinase-1 (ALK-1) homolog. Wu, X., Robinson, C.E., Fong, H.W., Crabtree, J.S., Rodriguez, B.R., Roe, B.A., Gimble, J.M. Biochem. Biophys. Res. Commun. (1995) [Pubmed]
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