Growth differentiation factor
Growth differentiation factors (GDFs) are a subfamily of proteins belonging to the transforming growth factor beta superfamily that have functions predominantly in development.[1]
Additional recommended knowledge
Types
Several members of this subfamily have been described, and named GDF1 through GDF15.
- GDF1 is chiefly expressed in the nervous system and functions in left-right patterning and mesoderm induction during embryonic development.[2]
- GDF2 (also known as BMP9) induces and maintains the response embryonic basal forebrain cholinergic neurons (BFCN) have to a neurotransmitter called acetylcholine, and regulates iron metabolism by increasing levels of a protein called hepcidin.[3][4]
- GDF3 is also known as "Vg-related gene 2" (Vgr-2). Expression of GDF3 occurs in ossifying bone during embryonic development and in the thymus, spleen, bone marrow brain and adipose tissue of adults. It has a dual nature of function; it both inhibits and induces early stages of development in embryos.[5][6][7]
- GDF5 is expressed in the developing central nervous system, with roles in the development of joints and the skeleton, and increasing the survival of neurones that respond to a neurotransmitter called dopamine.[8][9][10]
- GDF6 interacts with bone morphogenetic proteins to regulate ectoderm patterning, and controls eye development.[11] [12][13]
- GDF8 is now officially known as myostatin and controls the growth of muscle tissue.[14]
- GDF9, like GDF3, lacks one cysteine relative to other members of the TGF-β superfamily. Its gene expression is limited to the ovaries and it has a role in ovulation.[15][16]
- GDF10 is closely related to BMP3 and has a roles in head formation and possibly in skeletal morphogenesis.[17][18] It is also known as BMP-3b.
- GDF11 controls anterior-posterior patterning by regulating the expression of Hox genes,[19] and regulates the number of olfactory receptor neurons occurring in the olfactory epithelium,[20] and numbers of retinal ganglionic cells developing in the retina.[21]
- GDF15 (also known as TGF-PL, MIC-1, PDF, PLAB, and PTGFB) has a role in regulating inflammatory and apoptotic pathways during tissue injury and certain disease processes.[22] [23][24]
References
- ^ Herpin A, Lelong C, Favrel P (2004). "Transforming growth factor-beta-related proteins: an ancestral and widespread superfamily of cytokines in metazoans". Dev Comp Immunol 28 (5): 461-85. PMID 15062644.
- ^ Rankin C, Bunton T, Lawler A, Lee S (2000). "Regulation of left-right patterning in mice by growth/differentiation factor-1". Nat Genet 24 (3): 262-5. PMID 10700179.
- ^ 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 U S A 102 (19): 6984-9. 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 U S A 103 (27): 10289-93. PMID 16801541.
- ^ Levine A, Brivanlou A (2006). "GDF3 at the crossroads of TGF-beta signaling". Cell Cycle 5 (10): 1069-73. PMID 16721050.
- ^ Levine A, Brivanlou A (2006). "GDF3, a BMP inhibitor, regulates cell fate in stem cells and early embryos". Development 133 (2): 209-16. PMID 16339188.
- ^ Chen C, Ware S, Sato A, Houston-Hawkins D, Habas R, Matzuk M, Shen M, Brown C (2006). "The Vg1-related protein Gdf3 acts in a Nodal signaling pathway in the pre-gastrulation mouse embryo". Development 133 (2): 319-29. PMID 16368929.
- ^ O'Keeffe G, Dockery P, Sullivan A (2004). "Effects of growth/differentiation factor 5 on the survival and morphology of embryonic rat midbrain dopaminergic neurones in vitro". J Neurocytol 33 (5): 479-88. PMID 15906156.
- ^ Buxton P, Edwards C, Archer C, Francis-West P (2001). "Growth/differentiation factor-5 (GDF-5) and skeletal development". J Bone Joint Surg Am 83-A Suppl 1 (Pt 1): S23-30. PMID 11263662.
- ^ Francis-West P, Parish J, Lee K, Archer C (1999). "BMP/GDF-signalling interactions during synovial joint development". Cell Tissue Res 296 (1): 111-9. PMID 10199971.
- ^ Chang C, Hemmati-Brivanlou A (1999). "Xenopus GDF6, a new antagonist of noggin and a partner of BMPs". Development 126 (15): 3347-57. PMID 10393114.
- ^ Asai-Coakwell M, French C, Berry K, Ye M, Koss R, Somerville M, Mueller R, van Heyningen V, Waskiewicz A, Lehmann O (2007). "GDF6, a novel locus for a spectrum of ocular developmental anomalies". Am J Hum Genet 80 (2): 306-15. PMID 17236135.
- ^ Hanel M, Hensey C. "Eye and neural defects associated with loss of GDF6". BMC Dev Biol 6: 43. PMID 17010201.
- ^ McPherron AC, Lawler AM, Lee SJ. Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member. Nature 1997;387:83-90. PMID 9139826.
- ^ Juengel J, Bodensteiner K, Heath D, Hudson N, Moeller C, Smith P, Galloway S, Davis G, Sawyer H, McNatty K. "Physiology of GDF9 and BMP15 signalling molecules". Anim Reprod Sci 82-83: 447-60. PMID 15271472.
- ^ Hreinsson J, Scott J, Rasmussen C, Swahn M, Hsueh A, Hovatta O (2002). "Growth differentiation factor-9 promotes the growth, development, and survival of human ovarian follicles in organ culture". J Clin Endocrinol Metab 87 (1): 316-21. PMID 11788667.
- ^ Hino J, Kangawa K, Matsuo H, Nohno T, Nishimatsu S. "Bone morphogenetic protein-3 family members and their biological functions". Front Biosci 9: 1520-9. PMID 14977563.
- ^ Cunningham N, Jenkins N, Gilbert D, Copeland N, Reddi A, Lee S (1995). "Growth/differentiation factor-10: a new member of the transforming growth factor-beta superfamily related to bone morphogenetic protein-3". Growth Factors 12 (2): 99-109. PMID 8679252.
- ^ Andersson O, Reissmann E, Ibáñez C (2006). "Growth differentiation factor 11 signals through the transforming growth factor-beta receptor ALK5 to regionalize the anterior-posterior axis". EMBO Rep 7 (8): 831-7. PMID 16845371.
- ^ Wu H, Ivkovic S, Murray R, Jaramillo S, Lyons K, Johnson J, Calof A (2003). "Autoregulation of neurogenesis by GDF11". Neuron 37 (2): 197-207. PMID 12546816.
- ^ Kim J, Wu H, Lander A, Lyons K, Matzuk M, Calof A (2005). "GDF11 controls the timing of progenitor cell competence in developing retina". Science 308 (5730): 1927-30. PMID 15976303.
- ^ Zimmers T, Jin X, Hsiao E, McGrath S, Esquela A, Koniaris L (2005). "Growth differentiation factor-15/macrophage inhibitory cytokine-1 induction after kidney and lung injury". Shock 23 (6): 543-8. PMID 15897808.
- ^ Hsiao E, Koniaris L, Zimmers-Koniaris T, Sebald S, Huynh T, Lee S (2000). "Characterization of growth-differentiation factor 15, a transforming growth factor beta superfamily member induced following liver injury". Mol Cell Biol 20 (10): 3742-51. PMID 10779363.
- ^ Ago T, Sadoshima J (2006). "GDF15, a cardioprotective TGF-beta superfamily protein". Circ Res 98 (3): 294-7. PMID 16484622.
| Cell signaling: TGF beta signaling pathway |
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| 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 A and B/Inhibin A and B, Anti-müllerian hormone, Nodal) |
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| TGF beta receptors | TGFBR1: Activin type 1 receptors (ACVR1, ACVR1B, ACVR1C) - ACVRL1 - BMPR1 (BMPR1A - BMPR1B)
TGFBR2: Activin type 2 receptors (ACVR2A, ACVR2B) - AMHR2 - BMPR2
TGFBR3: betaglycan |
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| Transducers/SMAD | R-SMAD (SMAD1, SMAD2, SMAD3, SMAD5, SMAD9) - I-SMAD (SMAD6, SMAD7) - SMAD4 |
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| Ligand Inhibitors | Cerberus - Chordin - DAN - Decorin - Follistatin - Gremlin - Lefty - LTBP1 - Noggin - THBS1 |
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| Coreceptors | BAMBI - Cripto |
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| Other | SARA |
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