GDF2

From Wikipedia, the free encyclopedia

Growth differentiation factor 2

PDB rendering based on 1zkz.

Available structures

Ortholog search: PDBe, RCSB

List of PDB id codes
1ZKZ, 4FAO

Identifiers

Symbols

GDF2; BMP-9; BMP9

External IDs

OMIM: 605120 MGI: 1321394 HomoloGene: 32299 GeneCards: GDF2 Gene

Gene Ontology
Molecular function	• cytokine activity • protein binding • growth factor activity
Cellular component	• extracellular space
Biological process	• ossification • patterning of blood vessels • vasculogenesis • osteoblast differentiation • negative regulation of endothelial cell proliferation • positive regulation of endothelial cell proliferation • cellular iron ion homeostasis • negative regulation of DNA replication • negative regulation of endothelial cell migration • positive regulation of pathway-restricted SMAD protein phosphorylation • negative regulation of angiogenesis • negative regulation of cell growth • BMP signaling pathway • positive regulation of BMP signaling pathway • positive regulation of interleukin-8 production • activin receptor signaling pathway • growth • negative regulation of blood vessel endothelial cell migration • positive regulation of endothelial cell differentiation • positive regulation of osteoblast differentiation • positive regulation of angiogenesis • positive regulation of transcription, DNA-dependent • positive regulation of transcription from RNA polymerase II promoter • blood vessel morphogenesis • cartilage development • pathway-restricted SMAD protein phosphorylation • negative regulation of DNA biosynthetic process
Sources: Amigo / QuickGO

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

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]

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.^[5]

References

↑ 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.
↑ 2.0 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.
↑ 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.
↑ 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.
↑ 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.

Davila S, Froeling FE, Tan A, et al. (2010). "New genetic associations detected in a host response study to hepatitis B vaccine.". Genes Immun. 11 (3): 232–8. doi:10.1038/gene.2010.1. PMID 20237496.
David L, Mallet C, Keramidas M, et al. (2008). "Bone morphogenetic protein-9 is a circulating vascular quiescence factor.". Circ. Res. 102 (8): 914–22. doi:10.1161/CIRCRESAHA.107.165530. PMC 2561062. PMID 18309101.
Herrera B, van Dinther M, Ten Dijke P, Inman GJ (2009). "Autocrine bone morphogenetic protein-9 signals through activin receptor-like kinase-2/Smad1/Smad4 to promote ovarian cancer cell proliferation.". Cancer Res. 69 (24): 9254–62. doi:10.1158/0008-5472.CAN-09-2912. PMC 2892305. PMID 19996292.
Upton PD, Davies RJ, Trembath RC, Morrell NW (2009). "Bone morphogenetic protein (BMP) and activin type II receptors balance BMP9 signals mediated by activin receptor-like kinase-1 in human pulmonary artery endothelial cells.". J. Biol. Chem. 284 (23): 15794–804. doi:10.1074/jbc.M109.002881. PMC 2708876. PMID 19366699.
Grupe A, Li Y, Rowland C, et al. (2006). "A scan of chromosome 10 identifies a novel locus showing strong association with late-onset Alzheimer disease.". Am. J. Hum. Genet. 78 (1): 78–88. doi:10.1086/498851. PMC 1380225. PMID 16385451.
Brown MA, Zhao Q, Baker KA, et al. (2005). "Crystal structure of BMP-9 and functional interactions with pro-region and receptors.". J. Biol. Chem. 280 (26): 25111–8. doi:10.1074/jbc.M503328200. PMID 15851468.
LÃ³pez-Coviella I, Berse B, Krauss R, et al. (2000). "Induction and maintenance of the neuronal cholinergic phenotype in the central nervous system by BMP-9.". Science 289 (5477): 313–6. doi:10.1126/science.289.5477.313. PMID 10894782.
Sharff KA, Song WX, Luo X, et al. (2009). "Hey1 basic helix-loop-helix protein plays an important role in mediating BMP9-induced osteogenic differentiation of mesenchymal progenitor cells.". J. Biol. Chem. 284 (1): 649–59. doi:10.1074/jbc.M806389200. PMC 2610517. PMID 18986983.
GratacÃ²s M, Costas J, de Cid R, et al. (2009). "Identification of new putative susceptibility genes for several psychiatric disorders by association analysis of regulatory and non-synonymous SNPs of 306 genes involved in neurotransmission and neurodevelopment.". Am. J. Med. Genet. B Neuropsychiatr. Genet. 150B (6): 808–16. doi:10.1002/ajmg.b.30902. PMID 19086053.
Ye L, Kynaston H, Jiang WG (2008). "Bone morphogenetic protein-9 induces apoptosis in prostate cancer cells, the role of prostate apoptosis response-4.". Mol. Cancer Res. 6 (10): 1594–606. doi:10.1158/1541-7786.MCR-08-0171. PMID 18922975.
Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
Majumdar MK, Wang E, Morris EA (2001). "BMP-2 and BMP-9 promotes chondrogenic differentiation of human multipotential mesenchymal cells and overcomes the inhibitory effect of IL-1.". J. Cell. Physiol. 189 (3): 275–84. doi:10.1002/jcp.10025. PMID 11748585.
Roberts KE, Kawut SM, Krowka MJ, et al. (2010). "Genetic risk factors for hepatopulmonary syndrome in patients with advanced liver disease.". Gastroenterology 139 (1): HASH(0x14ea320). doi:10.1053/j.gastro.2010.03.044. PMC 2908261. PMID 20346360.
Strausberg RL, Feingold EA, Grouse LH, et al. (2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Takahashi T, Morris EA, Trippel SB (2007). "Bone morphogenetic protein-2 and -9 regulate the interaction of insulin-like growth factor-I with growth plate chondrocytes.". Int. J. Mol. Med. 20 (1): 53–7. PMID 17549388.
Scharpfenecker M, van Dinther M, Liu Z, et al. (2007). "BMP-9 signals via ALK1 and inhibits bFGF-induced endothelial cell proliferation and VEGF-stimulated angiogenesis.". J. Cell. Sci. 120 (Pt 6): 964–72. doi:10.1242/jcs.002949. PMID 17311849.

Cell signaling: TGF beta signaling pathway

TGF beta superfamily of ligands

TGF beta family	TGF-β1 TGF-β2 TGF-β3

Bone morphogenetic proteins	BMP2 BMP3 BMP4 BMP5 BMP6 BMP7 BMP8a BMP8b BMP10 BMP15

Growth differentiation factors	GDF1 GDF2 GDF3 GDF5 GDF6 GDF7 Myostatin/GDF8 GDF9 GDF10 GDF11 GDF15

Other	Activin and inhibin Anti-müllerian hormone Nodal

TGF beta receptors
(Activin, BMP)

TGFBR1:	Activin type 1 receptors ACVR1 ACVR1B ACVR1C ACVRL1 BMPR1 BMPR1A BMPR1B

TGFBR2:	Activin type 2 receptors ACVR2A ACVR2B AMHR2 BMPR2

TGFBR3:	betaglycan

Transducers/SMAD

Ligand inhibitors

Coreceptors

BAMBI
Cripto

Other

SARA

B trdu: iter (nrpl/grfl/cytl/horl), csrc (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd; path (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)

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GDF2

Function

References

Further reading