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Growth differentiation factor 2
PDB 1zkz EBI.png
PDB rendering based on 1zkz.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols GDF2 ; BMP-9; BMP9
External IDs OMIM605120 MGI1321394 HomoloGene32299 GeneCards: GDF2 Gene
Species Human Mouse
Entrez 2658 12165
Ensembl ENSG00000128802 ENSMUSG00000072625
UniProt Q9UK05 Q9WV56
RefSeq (mRNA) NM_016204 NM_019506
RefSeq (protein) NP_057288 NP_062379
Location (UCSC) Chr 10:
48.41 – 48.42 Mb
Chr 14:
33.94 – 33.95 Mb
PubMed search [1] [2]

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.


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]


  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. ^ a b 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/ PMID 15269709. 

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