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FLASH GENE
Symbol GDF2 contributors: mct/pgu - updated : 16-10-2013
HGNC name growth differentiation factor 2
HGNC id 4217
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • TGF beta-like domain
  • mono polymer homomer , dimer
    isoforms Precursor cleaved at a consensus Arg-X-XArg to yield a C terminus mature dimer
    HOMOLOGY
    Homologene
    FAMILY
  • BMP family
  • TGF-beta family
  • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION extracellular
    text secreted
    basic FUNCTION
  • differentiation of cholinergic central nervous system neurons
  • potent synergistic factor for hematopoietic progenitor-cell generation and colony formation and may play a role in the induction and maintenance of the neuronal cholinergic phenotype in the central nervous system
  • may function as a tumor suppressor and apoptosis regulator in prostate cancer
  • circulating under a biologically active form, is a potent antiangiogenic factor that is likely to play a physiological role in the control of adult blood vessel quiescence
  • potent antiangiogenic factor that is likely to play a physiological role in the control of adult blood vessel quiescence
  • potently induces osteogenesis and chondrogenesis, has been implicated in the differentiation of cholinergic neurons, and may help regulate glucose metabolism
  • inducing Smad1/5 phosphorylation in human pulmonary artery endothelial cells, also stimulating Smad2 activation and inducing the expression of interleukin 8 and E-selectin
  • specifically plays a physiologic role in the control of adult blood-vessel maintenance and angiogenesis by targeting ALK1 on endothelial cells
  • cholinergic differentiating factor during development
  • mutual regulation by GDF2 and BMPER is essential in regulating the development of the vascular endothelium
  • GDF2 and BMP10 are important in postnatal vascular remodeling of the retina and BMP10 can substitute for GDF2
  • TMEM100 may play indispensable roles downstream of GDF2/BMP10-ACVRL1 signaling during endothelial differentiation and vascular morphogenesis
  • implicated in regulation of the CXCL12/CXCR4 chemokine axis in endothelial cells (PMID;
  • GDF2 signaling may be relevant during hepatocarcinogenesis
  • exogenous CRELD2 promotes GDF2-induced ectopic bone formation and matrix mineralization, whereas silencing CRELD2 expression diminishes GDF2-induced bone formation and matrix mineralization
  • CELLULAR PROCESS cell life, differentiation
    PHYSIOLOGICAL PROCESS development
    text promoting chondrogenic differentiation of multipotential mesenchymal cells
    PATHWAY
    metabolism
    signaling
    a component
  • autocrine/paracrine mediator in the hepatic reticulo-endothelial system
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • overcoming the inhibitory effect of IL-1 on chondrogenic differentiation
  • with BMP10, are specific ligands for ACVRL1 that potently inhibit microvascular endothelial cell migration and growth
  • interacting with HEY1 (HEY1 expression was significantly up-regulated at the immediate early stage of GDF2 stimulation coinciding with the commitment of mesenchymal stem cells to osteoblast lineage)
  • GDF2 crosstalks with IGF2 through PI3K/AKT signaling pathway during osteogenic differentiation of MSCs
  • GDF2 induced EDN1 release is involved in both inhibition of endothelial cell migration and promotion of tubule formation
  • high specificity of ACVRL1 for GDF2/BMP10 is determined by a novel orientation of ACVRL1 with respect to GDF2, which leads to a unique set of receptor-ligand interactions
  • TMEM100 is a embryonic endothelium-enriched gene activated by GDF2 and BMP10 through ACVRL1
  • GDF2 and BMP10 are the physiological, functionally equivalent ligands of ACVRL1 in vascular development
  • may effectively overcome noggin inhibition, which should at least in part contribute to GDF2 potent osteogenic capability in MSCs
  • PTGS2 plays an important role in GDF2 induced osteogenic differentiation in mesenchymal stem cells
  • histone deacetylases may play an important role in fine-tuning GDF2-mediated osteogenic signaling through a negative feedback network in mesenchymal stem cells
  • activation of JNKs is essential for GDF2 osteoinductive activity
  • CRELD2 may be directly regulated by GDF2
  • GDF2 inhibits lymphatic vessel formation via ACVRL1 during development and cancer progression
  • GDF2 and BMP10 enhance TNF-induced monocyte recruitment to the vascular endothelium mainly via ACVR1
  • cell & other
    REGULATION
    activated by cleaved by subtilisin-like convertases
    ASSOCIATED DISORDERS
    corresponding disease(s) ORW6
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral        
    in prostate cancer, particularly in the foci of higher grade disease
    tumoral     --over  
    in 40p100 of hepatocellular carcinoma cells tissues compared with normal human liver
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    osteoarticularboneostéoporosis
    combination of GDF2 and IGF2 may be explored as an effective bone-regeneration agent to treat large segmental bony defects, nonunion fracture, and/or osteoporotic fracture
    ANIMAL & CELL MODELS