ACVR1: Difference between revisions
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A mutation in the gene ACVR1 (= ALK2) is responsible for the [[fibrodysplasia ossificans progressiva]].<ref name="ACVR1">{{cite journal |author=Shore EM |title=A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva |journal=Nat. Genet. |volume=38 |issue=5 |pages=525–527 |year=2006 |pmid=16642017 |doi=10.1038/ng1783 |url=http://www.nature.com/ng/journal/v38/n5/abs/ng1783.html |author-separator=, |author2=Xu M |author3=Feldman GJ |display-authors=3 |last4=Fenstermacher |first4=David A |last5=Brown |first5=Matthew A |last6=Kaplan |first6=Frederick S |last7=Connor |first7=JM |last8=Delai |first8=P |last9=Glaser |first9=DL}}</ref> ACVR1 encodes [[activin]] receptor type-1, a [[Bone morphogenetic protein|BMP]] type-1 receptor. The mutation causes the ACVR1 protein to have the amino acid histidine substituted for the amino acid arginine at position 206.<ref>[http://www.uphs.upenn.edu/news/News_Releases/apr06/FOP.htm News Release of FOP's Cause]</ref> This causes [[endothelial cell]]s to transform to [[mesenchymal stem cell]]s and then to bone.<ref>{{cite journal |title=ALK2 R206H mutation linked to fibrodysplasia ossificans progressiva confers constitutive activity to the BMP type I receptor and sensitizes mesenchymal cells to BMP-induced osteoblast differentiation and bone formation |doi=10.1359/jbmr.091110 |year=2010 |author=Dinther |last2=Visser |first2=Nils |last3=De Gorter |first3=David JJ |last4=Doorn |first4=Joyce |last5=Goumans |first5=Marie-José |last6=De Boer |first6=Jan |last7=Ten Dijke |first7=Peter |journal=Journal of Bone and Mineral Research |pages=091211115834058–35 |display-authors=1 }}</ref> |
A mutation in the gene ACVR1 (= ALK2) is responsible for the [[fibrodysplasia ossificans progressiva]].<ref name="ACVR1">{{cite journal |author=Shore EM |title=A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva |journal=Nat. Genet. |volume=38 |issue=5 |pages=525–527 |year=2006 |pmid=16642017 |doi=10.1038/ng1783 |url=http://www.nature.com/ng/journal/v38/n5/abs/ng1783.html |author-separator=, |author2=Xu M |author3=Feldman GJ |display-authors=3 |last4=Fenstermacher |first4=David A |last5=Brown |first5=Matthew A |last6=Kaplan |first6=Frederick S |last7=Connor |first7=JM |last8=Delai |first8=P |last9=Glaser |first9=DL}}</ref> ACVR1 encodes [[activin]] receptor type-1, a [[Bone morphogenetic protein|BMP]] type-1 receptor. The mutation causes the ACVR1 protein to have the amino acid histidine substituted for the amino acid arginine at position 206.<ref>[http://www.uphs.upenn.edu/news/News_Releases/apr06/FOP.htm News Release of FOP's Cause]</ref> This causes [[endothelial cell]]s to transform to [[mesenchymal stem cell]]s and then to bone.<ref>{{cite journal |title=ALK2 R206H mutation linked to fibrodysplasia ossificans progressiva confers constitutive activity to the BMP type I receptor and sensitizes mesenchymal cells to BMP-induced osteoblast differentiation and bone formation |doi=10.1359/jbmr.091110 |year=2010 |author=Dinther |last2=Visser |first2=Nils |last3=De Gorter |first3=David JJ |last4=Doorn |first4=Joyce |last5=Goumans |first5=Marie-José |last6=De Boer |first6=Jan |last7=Ten Dijke |first7=Peter |journal=Journal of Bone and Mineral Research |pages=091211115834058–35 |display-authors=1 }}</ref> |
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Four studies appeared Nature Genetics (April 2014)linked recurring mutations in ACVR1 to cancer for the first time. These studies were of particular note for patients diagnosed with a subtype of High Grade Glioma (HGG) called diffuse intrinsic pontine glioma (DIPG). <ref>http://www.curebraincancer.org.au/news/1044/multiple-breakthroughs-in-childhood-brain-cancer</ref> |
Four studies appeared Nature Genetics (April 2014) linked recurring mutations in ACVR1 to cancer for the first time. These studies were of particular note for patients diagnosed with a subtype of High Grade Glioma (HGG) called [[diffuse intrinsic pontine glioma ]](DIPG). <ref>http://www.curebraincancer.org.au/news/1044/multiple-breakthroughs-in-childhood-brain-cancer</ref> |
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==References== |
==References== |
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Revision as of 15:40, 11 April 2014
Activin A receptor, type I (ACVR1) also known as ALK-2 is a protein which in humans is encoded by the ACVR1 gene.[1]
Function
Activins are dimeric growth and differentiation factors which belong to the transforming growth factor-beta (TGF beta) superfamily of structurally related signaling proteins. Activins signal through a heteromeric complex of receptor serine kinases which include at least two type I ( I and IB) and two type II (II and IIB) receptors. These receptors are all transmembrane proteins, composed of a ligand-binding extracellular domain with cysteine-rich region, a transmembrane domain, and a cytoplasmic domain with predicted serine/threonine specificity. Type I receptors are essential for signaling; and type II receptors are required for binding ligands and for expression of type I receptors. Type I and II receptors form a stable complex after ligand binding, resulting in phosphorylation of type I receptors by type II receptors. This gene encodes activin A type I receptor which signals a particular transcriptional response in concert with activin type II receptors.[2]
Signaling
ACVR1 transduces signals of BMPs. BMPs bind either ACVR2A/ACVR2B or a BMPR2 and then form a complex with ACVR1. These go on to recruit the R-SMADs SMAD1, SMAD2, SMAD3 or SMAD6.[3]
Clinical significance
A mutation in the gene ACVR1 (= ALK2) is responsible for the fibrodysplasia ossificans progressiva.[4] ACVR1 encodes activin receptor type-1, a BMP type-1 receptor. The mutation causes the ACVR1 protein to have the amino acid histidine substituted for the amino acid arginine at position 206.[5] This causes endothelial cells to transform to mesenchymal stem cells and then to bone.[6]
Four studies appeared Nature Genetics (April 2014) linked recurring mutations in ACVR1 to cancer for the first time. These studies were of particular note for patients diagnosed with a subtype of High Grade Glioma (HGG) called diffuse intrinsic pontine glioma (DIPG). [7]
References
- ^ ten Dijke P, Ichijo H, Franzén P, Schulz P, Saras J, Toyoshima H, Heldin CH, Miyazono K (October 1993). "Activin receptor-like kinases: a novel subclass of cell-surface receptors with predicted serine/threonine kinase activity". Oncogene. 8 (10): 2879–87. PMID 8397373.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ "Entrez Gene: ACVR1 (activin A receptor, type I)".
- ^ Inman GJ, Nicolás FJ, Callahan JF, Harling JD, Gaster LM, Reith AD, Laping NJ, Hill CS (July 2002). "SB-431542 is a potent and specific inhibitor of transforming growth factor-beta superfamily type I activin receptor-like kinase (ALK) receptors ALK4, ALK5, and ALK7". Molecular Pharmacology. 62 (1): 65–74. doi:10.1124/mol.62.1.65. PMID 12065756.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Shore EM; Xu M; Feldman GJ; et al. (2006). "A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva". Nat. Genet. 38 (5): 525–527. doi:10.1038/ng1783. PMID 16642017.
{{cite journal}}: Unknown parameter|author-separator=ignored (help) - ^ News Release of FOP's Cause
- ^ Dinther; et al. (2010). "ALK2 R206H mutation linked to fibrodysplasia ossificans progressiva confers constitutive activity to the BMP type I receptor and sensitizes mesenchymal cells to BMP-induced osteoblast differentiation and bone formation". Journal of Bone and Mineral Research: 091211115834058–35. doi:10.1359/jbmr.091110.
- ^ http://www.curebraincancer.org.au/news/1044/multiple-breakthroughs-in-childhood-brain-cancer
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
