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Bone morphogenetic protein 4

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Template:PBB Bone morphogenetic protein 4 is a protein that in humans is encoded by BMP4 gene.[1][2]

BMP4 is a member of the bone morphogenetic protein family which is part of the transforming growth factor-beta superfamily. The superfamily includes large families of growth and differentiation factors.

History

Bone morphogenetic proteins were originally identified by an ability of demineralized bone extract to induce endochondral osteogenesis in vivo in an extraskeletal site.

Function

This particular family member plays an important role in the onset of endochondral bone formation in humans. It has been shown to be involved in muscle development, bone mineralization, and ureteric bud development.

In human embryonic development, BMP4 is a critical signaling molecule required for the early differentiation of the embryo and establishing of a dorsal-ventral axis. BMP4 is secreted from the dorsal portion of the notochord, and it acts in concert with sonic hedgehog (released from the ventral portion of the notochord) to establish a dorsal-ventral axis for the differentiation of later structures.

BMP4 stimulates differentiation of overlying ectodermal tissue.

Inhibition

Inhibition of the BMP4 signal (by chordin, noggin, or follistatin) causes the ectoderm to differentiate into the neural plate. If these cells also receive signals from FGF, they will differentiate into the spinal cord; in the absence of FGF the cells become brain tissue.

Configurations

Alternative splicing in the 5' untranslated region of this gene has been described and three variants are described, all encoding an identical protein.[3]

BMP4 is a polypeptide belonging to the TGF-β superfamily of proteins. It, like other bone morphogenetic proteins, is involved in bone and cartilage development, specifically tooth and limb development and fracture repair.

Disease

Increase in expression of BMP4 has been associated with a variety of bone diseases, including the heritable disorder Fibrodysplasia Ossificans Progressiva.[4]

There is strong evidence from sequencing studies of candidate genes involved in clefting that mutations in the bone morphogenetic protein 4 (BMP4) gene may be associated in the pathogenesis of cleft lip and palate.[5]

References

  1. ^ van den Wijngaard A, Weghuis DO, Boersma CJ, van Zoelen EJ, Geurts van Kessel A, Olijve W (1995). "Fine mapping of the human bone morphogenetic protein-4 gene (BMP4) to chromosome 14q22-q23 by in situ hybridization". Genomics. 27 (3): 559–60. doi:10.1006/geno.1995.1096. PMID 7558046. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  2. ^ Oida S, Iimura T, Maruoka Y, Takeda K, Sasaki S (1995). "Cloning and sequence of bone morphogenetic protein 4 (BMP-4) from a human placental cDNA library". DNA Seq. 5 (5): 273–5. PMID 7579580. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  3. ^ "Entrez Gene: BMP4 bone morphogenetic protein 4".
  4. ^ Kan L, Hu M, Gomes WA, Kessler JA (2004). "Transgenic Mice Overexpressing BMP4 Develop a Fibrodysplasia Ossificans Progressiva (FOP)-Like Phenotype". Am. J. Pathol. 165 (4): 1107–15. doi:10.1016/S0002-9440(10)63372-X. PMC 1618644. PMID 15466378. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  5. ^ Dixon MJ, Marazita ML, Beaty TH, Murray JC (2011). "Cleft lip and palate: understanding genetic and environmental influences". Nat. Rev. Genet. 12 (3): 167–78. doi:10.1038/nrg2933. PMC 3086810. PMID 21331089. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)

Further reading

  • Wozney JM; Rosen V; Celeste AJ; et al. (1989). "Novel regulators of bone formation: molecular clones and activities". Science. 242 (4885): 1528–34. doi:10.1126/science.3201241. PMID 3201241. {{cite journal}}: Unknown parameter |author-separator= ignored (help)
  • Rosenzweig BL; Imamura T; Okadome T; et al. (1995). "Cloning and characterization of a human type II receptor for bone morphogenetic proteins". Proc. Natl. Acad. Sci. U.S.A. 92 (17): 7632–6. doi:10.1073/pnas.92.17.7632. PMC 41199. PMID 7644468. {{cite journal}}: Unknown parameter |author-separator= ignored (help)
  • Nohno T; Ishikawa T; Saito T; et al. (1995). "Identification of a human type II receptor for bone morphogenetic protein-4 that forms differential heteromeric complexes with bone morphogenetic protein type I receptors". J. Biol. Chem. 270 (38): 22522–6. doi:10.1074/jbc.270.38.22522. PMID 7673243. {{cite journal}}: Unknown parameter |author-separator= ignored (help)CS1 maint: unflagged free DOI (link)
  • Yamaji N; Celeste AJ; Thies RS; et al. (1995). "A mammalian serine/threonine kinase receptor specifically binds BMP-2 and BMP-4". Biochem. Biophys. Res. Commun. 205 (3): 1944–51. doi:10.1006/bbrc.1994.2898. PMID 7811286. {{cite journal}}: Unknown parameter |author-separator= ignored (help)
  • Harris SE; Harris MA; Mahy P; et al. (1994). "Expression of bone morphogenetic protein messenger RNAs by normal rat and human prostate and prostate cancer cells". Prostate. 24 (4): 204–11. doi:10.1002/pros.2990240406. PMID 8146069. {{cite journal}}: Unknown parameter |author-separator= ignored (help)
  • van den Wijngaard A (1996). "Genomic organization of the human bone morphogenetic protein-4 gene: molecular basis for multiple transcripts". Biochem. Biophys. Res. Commun. 219 (3): 789–94. doi:10.1006/bbrc.1996.0312. PMID 8645259. {{cite journal}}: Invalid |display-authors=3 (help); Unknown parameter |author-separator= ignored (help)
  • Nishitoh H; Ichijo H; Kimura M; 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. PMID 8702914. {{cite journal}}: Unknown parameter |author-separator= ignored (help)CS1 maint: unflagged free DOI (link)
  • Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  • Shore EM; Xu M; Shah PB; et al. (1998). "The human bone morphogenetic protein 4 (BMP-4) gene: molecular structure and transcriptional regulation". Calcif. Tissue Int. 63 (3): 221–9. doi:10.1007/s002239900518. PMID 9701626. {{cite journal}}: |first8= has numeric name (help); Unknown parameter |author-separator= ignored (help)CS1 maint: extra punctuation (link) CS1 maint: multiple names: authors list (link)
  • Tucker AS, Matthews KL, Sharpe PT (1998). "Transformation of tooth type induced by inhibition of BMP signaling". Science. 282 (5391): 1136–8. doi:10.1126/science.282.5391.1136. PMID 9804553.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  • Van den Wijngaard A (1999). "Functional characterization of two promoters in the human bone morphogenetic protein-4 gene". J. Bone Miner. Res. 14 (8): 1432–41. doi:10.1359/jbmr.1999.14.8.1432. PMID 10457277. {{cite journal}}: Invalid |display-authors=3 (help); Unknown parameter |author-separator= ignored (help)
  • Li W, LoTurco JJ (2000). "Noggin is a negative regulator of neuronal differentiation in developing neocortex". Dev. Neurosci. 22 (1–2): 68–73. doi:10.1159/000017428. PMID 10657699.
  • Raatikainen-Ahokas A; Hytönen M; Tenhunen A; et al. (2000). "BMP-4 affects the differentiation of metanephric mesenchyme and reveals an early anterior-posterior axis of the embryonic kidney". Dev. Dyn. 217 (2): 146–58. doi:10.1002/(SICI)1097-0177(200002)217:2<146::AID-DVDY2>3.0.CO;2-I. PMID 10706139. {{cite journal}}: Unknown parameter |author-separator= ignored (help)
  • van den Wijngaard A (2000). "Antiestrogens specifically up-regulate bone morphogenetic protein-4 promoter activity in human osteoblastic cells". Mol. Endocrinol. 14 (5): 623–33. doi:10.1210/me.14.5.623. PMID 10809227. {{cite journal}}: Invalid |display-authors=3 (help); Unknown parameter |author-separator= ignored (help)
  • Ying Y; Liu XM; Marble A; et al. (2000). "Requirement of Bmp8b for the generation of primordial germ cells in the mouse". Mol. Endocrinol. 14 (7): 1053–63. doi:10.1210/me.14.7.1053. PMID 10894154. {{cite journal}}: Unknown parameter |author-separator= ignored (help)
  • Nakade O; Takahashi K; Takuma T; et al. (2001). "Effect of extracellular calcium on the gene expression of bone morphogenetic protein-2 and -4 of normal human bone cells". J. Bone Miner. Metab. 19 (1): 13–9. doi:10.1007/s007740170055. PMID 11156467. {{cite journal}}: Unknown parameter |author-separator= ignored (help)
  • Hatta T; Konishi H; Katoh E; et al. (2001). "Identification of the ligand-binding site of the BMP type IA receptor for BMP-4". Biopolymers. 55 (5): 399–406. doi:10.1002/1097-0282(2000)55:5<399::AID-BIP1014>3.0.CO;2-9. PMID 11241215. {{cite journal}}: Unknown parameter |author-separator= ignored (help)
  • Aoki H; Fujii M; Imamura T; et al. (2001). "Synergistic effects of different bone morphogenetic protein type I receptors on alkaline phosphatase induction". J. Cell. Sci. 114 (Pt 8): 1483–9. PMID 11282024. {{cite journal}}: Unknown parameter |author-separator= ignored (help)
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