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Gene Review

Bmpr1b  -  bone morphogenetic protein receptor, type 1B

Mus musculus

Synonyms: AI385617, ALK-6, AV355320, Activin receptor-like kinase 6, Acvrlk6, ...
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Disease relevance of Bmpr1b


High impact information on Bmpr1b

  • To determine the mechanisms underlying BMP actions, we analyzed the expression and function of two BMP receptors, BMPR-IA and BMPR-IB, in neural precursor cells in vitro and in vivo [4].
  • When BMPR-IB is activated, it limits precursor cell numbers by causing mitotic arrest [4].
  • Populations of rare CD34(+)CD38(-)Lin- stem cells were isolated from human hematopoietic tissue and were found to express the BMP type I receptors activin-like kinase (ALK)-3 and ALK-6, and their downstream transducers SMAD-1, -4, and -5 [5].
  • To determine the role of BMP receptor signaling in bone formation in vivo, we generated transgenic mice, which express a truncated dominant-negative BMPR-IB targeted to osteoblasts using the type I collagen promoter [6].
  • BMP-2-induced ALP activity could be rescued by transfection of wild-type (wt) BMPR-IB into 2T3 clones containing trBMPR-IB [7].

Chemical compound and disease context of Bmpr1b


Biological context of Bmpr1b


Anatomical context of Bmpr1b

  • In midgestation embryos, ALK-6 transcripts were detected in mesenchymal precartilage condensations, premuscle masses, blood vessels, central nervous system, parts of the developing ear and eye, and epithelium [12].
  • However, by immunohistochemistry we found that ALK-6 staining was strong in E14 early cartilage primordium and its future perichondrium but dropped sharply to low levels in these cell types until onset of chondrocyte (pre)hypertrophy at E16 [13].
  • Thus, ALK-2 and ALK-3 (or ALK-6) might synergistically induce osteoblast differentiation of C2C12 cells, possibly through efficient activation of downstream signaling pathways [14].
  • In normal rat adult bone, expression of BMPR-IA, but not of BMPR-IB, was observed in osteoblasts in the periosteum [15].
  • The reporter construct analysis, pattern of expression of the receptors, and analysis of ALK6-deficient animals suggest that ALK2 is the MIS type I receptor involved in Müllerian duct regression [16].

Associations of Bmpr1b with chemical compounds

  • Our data therefore demonstrate that the osteogenic commitment of multipotent mouse ADAS requires retinoic acid, which enhances expression of the critical BMPR-IB isoform [17].
  • RT-PCR analysis showed that the BMPR-IB message was upregulated by androgen stimulation in the LNCaP cell line which expresses the androgen receptor [2].
  • Together, our data suggest that a signal(s) from collagen integrin receptors regulates the response to BMP downstream of BMPR-IB and upstream of the regulation of ALP mRNA and other early markers of osteoblast differentiation [18].

Physical interactions of Bmpr1b


Other interactions of Bmpr1b

  • Whereas mice deficient in type 1 receptors Bmpr1a or Bmpr1b in cartilage are able to form intact cartilaginous elements, double mutants develop a severe generalized chondrodysplasia [8].
  • We therefore propose that the effects of OP-1 on these cells in vitro are mediated by ALK-6/BMPR-IB [13].
  • Moreover, the limb defects in Gli3(-/-);Plzf(-/-) embryos correlate with the transient death of a specific subset of proximal mesenchymal cells that express bone morphogenetic protein receptor, type 1B (Bmpr1b) at the onset of limb development [20].
  • ALK6 has been shown to function as an MIS type I receptor [16].
  • At the cap stage, BMPR-IB was detected in the epithelium but not BMPR-II, suggesting the existence of another type II receptor to form a functional dimer [21].

Analytical, diagnostic and therapeutic context of Bmpr1b


  1. Noggin overexpression inhibits eyelid opening by altering epidermal apoptosis and differentiation. Sharov, A.A., Weiner, L., Sharova, T.Y., Siebenhaar, F., Atoyan, R., Reginato, A.M., McNamara, C.A., Funa, K., Gilchrest, B.A., Brissette, J.L., Botchkarev, V.A. EMBO J. (2003) [Pubmed]
  2. Cloning of human bone morphogenetic protein type IB receptor (BMPR-IB) and its expression in prostate cancer in comparison with other BMPRs. Ide, H., Katoh, M., Sasaki, H., Yoshida, T., Aoki, K., Nawa, Y., Osada, Y., Sugimura, T., Terada, M. Oncogene (1997) [Pubmed]
  3. Differential expression of BMP receptors in early mouse development. Roelen, B.A., Goumans, M.J., van Rooijen, M.A., Mummery, C.L. Int. J. Dev. Biol. (1997) [Pubmed]
  4. Sequential actions of BMP receptors control neural precursor cell production and fate. Panchision, D.M., Pickel, J.M., Studer, L., Lee, S.H., Turner, P.A., Hazel, T.G., McKay, R.D. Genes Dev. (2001) [Pubmed]
  5. Bone morphogenetic proteins regulate the developmental program of human hematopoietic stem cells. Bhatia, M., Bonnet, D., Wu, D., Murdoch, B., Wrana, J., Gallacher, L., Dick, J.E. J. Exp. Med. (1999) [Pubmed]
  6. Bone morphogenetic protein receptor signaling is necessary for normal murine postnatal bone formation. Zhao, M., Harris, S.E., Horn, D., Geng, Z., Nishimura, R., Mundy, G.R., Chen, D. J. Cell Biol. (2002) [Pubmed]
  7. Differential roles for bone morphogenetic protein (BMP) receptor type IB and IA in differentiation and specification of mesenchymal precursor cells to osteoblast and adipocyte lineages. Chen, D., Ji, X., Harris, M.A., Feng, J.Q., Karsenty, G., Celeste, A.J., Rosen, V., Mundy, G.R., Harris, S.E. J. Cell Biol. (1998) [Pubmed]
  8. Bmpr1a and Bmpr1b have overlapping functions and are essential for chondrogenesis in vivo. Yoon, B.S., Ovchinnikov, D.A., Yoshii, I., Mishina, Y., Behringer, R.R., Lyons, K.M. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  9. Genetic analyses demonstrate that bone morphogenetic protein signaling is required for embryonic cerebellar development. Qin, L., Wine-Lee, L., Ahn, K.J., Crenshaw, E.B. J. Neurosci. (2006) [Pubmed]
  10. Combinatorial signaling through BMP receptor IB and GDF5: shaping of the distal mouse limb and the genetics of distal limb diversity. Baur, S.T., Mai, J.J., Dymecki, S.M. Development (2000) [Pubmed]
  11. The type I BMP receptor BMPRIB is required for chondrogenesis in the mouse limb. Yi, S.E., Daluiski, A., Pederson, R., Rosen, V., Lyons, K.M. Development (2000) [Pubmed]
  12. Distinct spatial and temporal expression patterns of two type I receptors for bone morphogenetic proteins during mouse embryogenesis. Dewulf, N., Verschueren, K., Lonnoy, O., Morén, A., Grimsby, S., Vande Spiegle, K., Miyazono, K., Huylebroeck, D., Ten Dijke, P. Endocrinology (1995) [Pubmed]
  13. Correlation between ALK-6 (BMPR-IB) distribution and responsiveness to osteogenic protein-1 (BMP-7) in embryonic mouse bone rudiments. Haaijman, A., Burger, E.H., Goei, S.W., Nelles, L., ten Dijke, P., Huylebroeck, D., Bronckers, A.L. Growth Factors (2000) [Pubmed]
  14. Synergistic effects of different bone morphogenetic protein type I receptors on alkaline phosphatase induction. Aoki, H., Fujii, M., Imamura, T., Yagi, K., Takehara, K., Kato, M., Miyazono, K. J. Cell. Sci. (2001) [Pubmed]
  15. Enhanced expression of type I receptors for bone morphogenetic proteins during bone formation. Ishidou, Y., Kitajima, I., Obama, H., Maruyama, I., Murata, F., Imamura, T., Yamada, N., ten Dijke, P., Miyazono, K., Sakou, T. J. Bone Miner. Res. (1995) [Pubmed]
  16. Müllerian inhibiting substance signaling uses a bone morphogenetic protein (BMP)-like pathway mediated by ALK2 and induces SMAD6 expression. Clarke, T.R., Hoshiya, Y., Yi, S.E., Liu, X., Lyons, K.M., Donahoe, P.K. Mol. Endocrinol. (2001) [Pubmed]
  17. Osteogenic differentiation of mouse adipose-derived adult stromal cells requires retinoic acid and bone morphogenetic protein receptor type IB signaling. Wan, D.C., Shi, Y.Y., Nacamuli, R.P., Quarto, N., Lyons, K.M., Longaker, M.T. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  18. Collagen integrin receptors regulate early osteoblast differentiation induced by BMP-2. Jikko, A., Harris, S.E., Chen, D., Mendrick, D.L., Damsky, C.H. J. Bone Miner. Res. (1999) [Pubmed]
  19. A single residue of GDF-5 defines binding specificity to BMP receptor IB. Nickel, J., Kotzsch, A., Sebald, W., Mueller, T.D. J. Mol. Biol. (2005) [Pubmed]
  20. Gli3 and Plzf cooperate in proximal limb patterning at early stages of limb development. Barna, M., Pandolfi, P.P., Niswander, L. Nature (2005) [Pubmed]
  21. Expression patterns of BMPRs in the developing mouse molar. Nadiri, A., Kuchler-Bopp, S., Perrin-Schmitt, F., Lesot, H. Cell Tissue Res. (2006) [Pubmed]
  22. Constitutively active BMP type I receptors transduce BMP-2 signals without the ligand in C2C12 myoblasts. Akiyama, S., Katagiri, T., Namiki, M., Yamaji, N., Yamamoto, N., Miyama, K., Shibuya, H., Ueno, N., Wozney, J.M., Suda, T. Exp. Cell Res. (1997) [Pubmed]
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