Recombinant Human Bone morphogenetic protein 4 (BMP4)

Function

Growth factor of the TGF-beta superfamily that plays essential roles in many developmental processes, including neurogenesis, vascular development, angiogenesis and osteogenesis (PubMed:31363885). Acts in concert with PTHLH/PTHRP to stimulate ductal outgrowth during embryonic mammary development and to inhibit hair follicle induction (By similarity). Initiates the canonical BMP signaling cascade by associating with type I receptor BMPR1A and type II receptor BMPR2 (PubMed:25868050, PubMed:8006002). Once all three components are bound together in a complex at the cell surface, BMPR2 phosphorylates and activates BMPR1A. In turn, BMPR1A propagates signal by phosphorylating SMAD1/5/8 that travel to the nucleus and act as activators and repressors of transcription of target genes (PubMed:25868050, PubMed:29212066). Positively regulates the expression of odontogenic development regulator MSX1 via inducing the IPO7-mediated import of SMAD1 to the nucleus (By similarity). Required for MSX1-mediated mesenchymal molar tooth bud development beyond the bud stage, via promoting Wnt signaling (By similarity). Acts as a positive regulator of odontoblast differentiation during mesenchymal tooth germ formation, expression is repressed during the bell stage by MSX1-mediated inhibition of CTNNB1 signaling (By similarity). Able to induce its own expression in dental mesenchymal cells and also in the neighboring dental epithelial cells via an MSX1-mediated pathway (By similarity). Can also signal through non-canonical BMP pathways such as ERK/MAP kinase, PI3K/Akt, or SRC cascades (PubMed:31363885). For example, induces SRC phosphorylation which, in turn, activates VEGFR2, leading to an angiogenic response (PubMed:31363885)

Subcellular Location

Secreted, extracellular space, extracellular matrix

Disease Association

Microphthalmia, syndromic, 6 (MCOPS6) : A disease characterized by microphthalmia/anophthalmia associated with facial, genital, skeletal, neurologic and endocrine anomalies. Microphthalmia is a disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues (anophthalmia). In many cases, microphthalmia/anophthalmia occurs in association with syndromes that include non-ocular abnormalities. [The disease is caused by variants affecting the gene represented in this entry] | Non-syndromic orofacial cleft 11 (OFC11) : A birth defect consisting of cleft lips with or without cleft palate. Cleft lips are associated with cleft palate in two-third of cases. A cleft lip can occur on one or both sides and range in severity from a simple notch in the upper lip to a complete opening in the lip extending into the floor of the nostril and involving the upper gum. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

Expressed in the lung and lower levels seen in the kidney. Present also in normal and neoplastic prostate tissues, and prostate cancer cell lines

Subunit

Homodimer; disulfide-linked (By similarity). Interacts with GREM2. Part of a complex consisting of TWSG1 and CHRD. Interacts with the serine proteases, HTRA1 and HTRA3; the interaction with either inhibits BMP4-mediated signaling. The HTRA protease activity is required for this inhibition (By similarity). Interacts with SOSTDC1. Interacts with FBN1 (via N-terminal domain) and FBN2 (PubMed:18339631). Interacts with type I receptor BMPR1A (PubMed:8006002). Interacts with type II receptor BMPR2 (PubMed:29212066). Interacts with FSTL1; this interaction inhibits the activation of the BMP4/Smad1/5/8 signaling pathway (PubMed:29212066). Interacts with SCUBE3 (PubMed:33308444). Interacts with TGFBR3 (PubMed:18184661)

• Wozney J.M. et al. Novel regulators of bone formation: molecular clones and activities. — Science (1988)
• Shore E.M. et al. The human bone morphogenetic protein 4 (BMP-4) gene: molecular structure and transcriptional regulation. — Calcif. Tissue Int. (1998)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Oida S. et al. Cloning and sequence of bone morphogenetic protein 4 (BMP-4) from a human placental cDNA library. — DNA Seq. (1995)
• ten Dijke P. et al. Identification of type I receptors for osteogenic protein-1 and bone morphogenetic protein-4. — J. Biol. Chem. (1994)
• Yanagita M. et al. USAG-1: a bone morphogenetic protein antagonist abundantly expressed in the kidney. — Biochem. Biophys. Res. Commun. (2004)
• Sengle G. et al. Targeting of bone morphogenetic protein growth factor complexes to fibrillin. — J. Biol. Chem. (2008)
• Kirkbride K.C. et al. Bone morphogenetic proteins signal through the transforming growth factor-beta type III receptor. — J. Biol. Chem. (2008)