GDF2

Growth differentiation factor 2

PDB rendering based on 1zkz.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
SymbolsGDF2 ; BMP-9; BMP9
External IDsOMIM: 605120 MGI: 1321394 HomoloGene: 32299 GeneCards: GDF2 Gene
Orthologs
SpeciesHumanMouse
Entrez265812165
EnsemblENSG00000128802ENSMUSG00000072625
UniProtQ9UK05Q9WV56
RefSeq (mRNA)NM_016204NM_019506
RefSeq (protein)NP_057288NP_062379
Location (UCSC)Chr 10:
48.41 – 48.42 Mb		Chr 14:
33.94 – 33.95 Mb
PubMed search

Growth differentiation factor 2 (GDF2) also known as bone morphogenetic protein (BMP)-9 is a protein that in humans is encoded by the GDF2 gene.[1] GDF2 belongs to the transforming growth factor beta superfamily.

Function

GDF2 has a role in inducing and maintaining the ability of embryonic basal forebrain cholinergic neurons (BFCN) to respond to a neurotransmitter called acetylcholine; BFCN are important for the processes of learning, memory and attention.[2] GDF2 is also important for the maturation of BFCN.[2] Another role of GDF2 has been recently suggested. GDF2 is a potent inducer of hepcidin (a cationic peptide that has antimicrobial properties) in liver cells (hepatocytes) and can regulate iron metabolism.[3] The physiological receptor of GDF2 is thought to be activin receptor-like kinase 1, ALK1 (also called ACVRL1), an endothelial-specific type I receptor of the TGF-beta receptor family.[4] Endoglin, a type I membrane glycoprotein that forms the TGF-beta receptor complex, is a co-receptor of ALK1 for GDF2/BMP-9 binding. Mutations in ALK1 and endoglin cause hereditary hemorrhagic telangiectasia (HHT), a rare but life-threatening genetic disorder that leads to abnormal blood vessel formation in multiple tissues and organs of the body. [5]

GDF2 is one of the most potent BMPs to induce orthotopic bone formation in vivo. BMP3, a blocker of most BMPs seems not to affect GDF2.[6]

References

  1. ↑ Miller AF, Harvey SA, Thies RS, Olson MS (June 2000). "Bone morphogenetic protein-9. An autocrine/paracrine cytokine in the liver". J. Biol. Chem. 275 (24): 17937–45. doi:10.1074/jbc.275.24.17937. PMID 10849432.
  2. ↑ 2.0 2.1 Lopez-Coviella I, Follettie M, Mellott T, Kovacheva V, Slack B, Diesl V, Berse B, Thies R, Blusztajn J (2005). "Bone morphogenetic protein 9 induces the transcriptome of basal forebrain cholinergic neurons". Proc Natl Acad Sci USA 102 (19): 6984–9. doi:10.1073/pnas.0502097102. PMC 1088172. PMID 15870197.
  3. ↑ Truksa J, Peng H, Lee P, Beutler E (2006). "Bone morphogenetic proteins 2, 4, and 9 stimulate murine hepcidin 1 expression independently of Hfe, transferrin receptor 2 (Tfr2), and IL-6". Proc Natl Acad Sci USA 103 (27): 10289–93. doi:10.1073/pnas.0603124103. PMC 1502450. PMID 16801541.
  4. ↑ David L, Mallet C, Mazerbourg S, Feige J, Bailly S (2007). "Identification of BMP9 and BMP10 as functional activators of the orphan activin receptor-like kinase 1, ALK1 (also called ACVRL1) in endothelial cells". Blood 109 (5): 1953–61. doi:10.1182/blood-2006-07-034124. PMID 17068149.
  5. ↑ McDonald J, Bayrak-Toydemir P, Pyeritz RE (2011). "Hereditary hemorrhagic telangiectasia: an overview of diagnosis, management, and pathogenesis". Genet Med 13 (7): 607–16. doi:10.1097/GIM.0b013e3182136d32. PMID 21546842.
  6. ↑ Q Kang, MH Sun, H Cheng, Y Peng, AG Montag, AT Deyrup, W Jiang, HH Luu, J Luo, JP Szatkowski, P Vanichakarn, JY Park, Y Li, RC Haydon and T-C He (2004). "Characterization of the distinct orthotopic bone-forming activity of 14 BMPs using recombinant adenovirus-mediated gene delivery". Gene Therapy 11 (17): 1312–20. doi:10.1038/sj.gt.3302298. PMID 15269709.


Further reading