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ACVRL1 (activin A receptor type II-like 1)

Abstract

Abstract Activin A receptor, type II-like kinase 1 (ALK1 is a serine-threonine kinase) predominantly expressed on endothelial cells surface. Mutations in its ACVRL1 encoding gene (12q11-14) cause type 2 Hereditary Haemorrhagic Telangiectasia (HHT2), an autosomal dominant multisystem vascular dysplasia. Its involvement in cancer neoangiogenesis has lead to the recent development of novel anti-cancer drugs, which are now in clinical trials.

Identity

Other namesACVRLK1
ALK-1
ALK1
HHT
HHT2
ORW2
SKR3
TSR-I
HGNC (Hugo) ACVRL1
LocusID (NCBI) 94
Location 12q13.13
Location_base_pair Starts at 52301202 and ends at 52317145 bp from pter ( according to hg19-Feb_2009)  [Mapping]

DNA/RNA

Note Starts at 52300692 and ends at 52307134 bp from pter (according to hg19- Feb_2009).
Description ACVRL1 is a protein coding gene and in human it is constituted by 10 exons. All exons but the first are coding exons. ACVRL1 transcript variants mRNA3 and mRNA4 include 11 exons, through the presence of a cryptic non-translated exon upstream of the canonical exon 1 (Garrido-Martin et al., 2010).
Transcription Gene database underlines the presence of two different ACVRL1 transcripts, which both translate into the same protein isoform. The second transcript variant is the shortest one and differs from the first one in the 5'UTR region, due to the presence of an upstream in-frame start codon, poorly conserved in the population. Nevertheless, in 2010 two new transcripts were discovered in HUVEC cells. These new variants, called mRNA3 and mRNA4, begin the transcription +1 nucleotide upstream , respectively at -510 and -470 positions, adding a cryptic non translated exon, that doesn't affect the protein ORF (Garrido-Martin et al., 2010).
The promoter region of ACVRL1 (5' proximal region: -1035/+210) was characterized by Garrido-Martin et al., 2010. This region lacks TATA/CAAT boxes but contains a high number of GC-rich Sp1 consensus sites. It also shares different putative regulatory elements with other endothelial-specific genes. These motifs includes: Ets (E26-Transformation-Specific), KLF (Krüppel-Like Factor), NFkB (Nuclear Factor kappa-light-chain-enhancer of activated B cells), E2F (Elongation Factor 2), one Smad binding element (SBE), RXR (Retinoid X Receptor) and HIF (Hypoxia Inducible Factor). Moreover, the authors demonstrated that methylation status of CpG islands modulates Sp1 transcription of ACVRL1 in endothelial cells.
In 2013, it has been demonstrated that ubiquitin E3 ligase, EDD, can down-regulate ACVRL1 expression in HeLa and HUVEC cells (Chien et al., 2013).

Protein

Description Activin A receptor, type II-like kinase 1 (also called ALK1, Uniprot entry P37023, protein family (pfam) 01064 of Activin types I and II receptor domains), is a serine-threonine kinase and it acts as a type I receptor for the Transforming Growth Factor-β / Bone Morphogenetic Protein (TGF-β/BMP) superfamily of ligands. It includes 503 amino acids, with residues 1-21 forming a leader sequence which targets the protein to the membrane. The extracellular domain includes amino acids 22-118 and it is followed by a 23 amino acid long transmembrane domain (residues 119-141). The intracellular domain comprises residues 142-503, with a GS domain (residues 172-201) and the protein kinase domain (residues 202-492).
The crystal structure of ALK1 ectodomain (Figure 1a) and of the intracellular kinase domain (Figure 1b) have been recently determined (PDB ID: 4FAO and 3MY0, respectively) (Townson et al., 2012).
Like all type I and type II receptors, ALK1 shows a general fold resembling a class of neurotoxins known as three-finger toxins and hence called "three-finger toxin fold". This fold is comprised from β-strands stabilised by disulphide bonds formed by conserved Cys residues. Three pairs of anti-parallel β-strands are curved to generate a concave surface. Despite the common architecture and the cluster of conserved Cys residues, very little sequence identity and no functional overlap exist between the two types of receptors.
BMPs consist of a Cys knot characterised by three pairs of highly conserved disulphide bonds in which one traverses through a ring formed by the other 2. This fold can be described as a hand with a concave palm side and two parallel β-sheet forming 4 fingers, with each β-strand being likened to a finger. Finger 2 leads to a helix "wrist" region. In the dimeric ligand the 4 fingers extend from the Cys core of the protein like butterfly wings. Binding of type I receptors occurs near the α-helix on the concave side at the junction between the two subunits (Kirsch et al., 2000), whereas binding to type II receptors happens on the convex side of the hand near the "fingertips" (Greenwald et al., 2003; Thompson et al., 2003).
 
  Figure 1: Structures of ALK1 ectodomain (a) and of the kinase domain (b).
Expression ALK1 is predominantly expressed on the endothelial cells surface of arteries. According to EBI gene expression database, ALK1 levels are reduced in non-small cell lung cancer tissue, and increased in monocytes exposed to infections by Francisella tularensis novocida and by Porphyromonas gengivalis.
Function ALK1 activation, triggered by its physiological ligand BMP-9, can be pro-angiogenic or anti-angiogenic, depending on the experimental system considered. Thus, inhibition of primary cells (HMVEC-D, HUVEC and endothelial cells) proliferation was observed upon activation of the receptor, suggesting that this signaling pathway is involved in the resolution phase of angiogenesis, during which endothelial cell proliferation and migration stop. Disruption of the pathway would therefore lead to persistent proliferation of endothelial cells with the lack of a correct morphogenesis.
On the other hand, MESEC (mouse embryonic- stem-cell-derived endothelial cells) and MEEC (mouse embryonic endothelial cells) cells are stimulated to proliferate by ALK1 activation and BMP9 stimulates angiogenesis in a matrigel plug assay and in a tumour model in vivo. Also, cancer cells produced tumours whose size and vascularization were reduced by 50% in ALK1+/- heterozygous mice compared with tumours implanted in wild-type littermates. In addition, a soluble ALK1-Fc fusion protein known as Dalantercept (ACE-041) showed an anti-angiogenic effect by reducing vascular density and perfusion of the tumour burden in model mice of endocrine pancreatic tumorigenesis and mice bearing 786-0 and A498 human renal cell carcinoma (Wang et al., 2012).
This contradictory findings may be explained by the site- and context-dependent balance of the synergic proangiogenic effects of BMP-9 and the lower affinity ALK1 ligand TGF-β, but the assumption has to be confirmed.
Recent studies also report a role for ALK1 in cancer independent from its effects on angiogenesis, enhancing the cell migration and invasion potential in cancers like squamous cell carcinomas of the head and the neck or haepatocarcinomas (Hu-Lowe et al., 2011; Chien et al., 2013; Sun et al., 2013).
ALK1 signalling through SMAD 1/SMAD 5/SMAD 8 seems to induce chondrocytes hypertrophy in cartilages by an effect mediated by the interaction with the canonical Wnt signaling (van den Bosch et al., 2014).
Again, in other kind of cancers ALK1 activation seems to be protective, as assessed for instance in in vitro models of pancreatic cancers (Ungefroren et al., 2007).
Homology ALK1 shares with other type I receptors a high degree of similarity in the GS domain, in the following serine-threonine kinase subdomains and in the short C-terminal tail (ten Dijke et al., 1994), but the extracellular domain shows a peculiar amino acidic sequence.

Mutations

Germinal Mutations in the ACVRL1 gene result in Hereditary Hemorrhagic Telangiectasia Type 2 (HHT2). A germinal mosaic with two mutant alleles in hereditary hemorrhagic telangiectasia associated with pulmonary arterial hypertension was described (Eyries et al., 2011,). A germline heterozygous ACVRL1 polymorphisms (p. A482V) has been reported in a patient with a gonadotroph pituitary tumour by D'Abronzo et al., 1999.
Somatic No somatic mutations of ACVRL1 have been found in human cancers.

Implicated in

Entity Solid tumours
Note As a receptor mainly expressed on the surface of endothelial cells, ALK1 overexpression and unbalances in its signalling are implicated in many solid tumours, despite the origin and specific features of the latter. Thus, they will be discussed in a single paragraph.
In a study (Hu-Lowe et al., 2011) performed on 3000 human tumour specimens representing more than 100 tumour types, ALK1 resulted particularly expressed in the vasculature of prostate cancers, malignant melanomas of the skin, follicular cancers of the tyroid, renal clear cell cancers and endometrioid ovarian cancers.
A reduced expression of ACVRL1 by qRT-PCR and immunohistochemistry was demonstrated in nasopharingeal carcinomas by Zhang et al., 2012.
An increased ALK1 expression in papillary thyroid carcinomas with bone formation was increased if compared to that in normal thyroid tissue and tumors without bone formation, as assessed using immunohistochemistry and quantitative real-time polymerase chain reaction (Na et al., 2013).
In Head and Neck Squamous Cell Carcinomas (HNSCC), using immunohistochemistry and qRT-PCR, Chien et al. found a correlation between a high ACVRL1 expression and an advanced T classification, a positive N classification, an advanced TNM stage, the presence of lymphovascular invasion, an extracapsular spread of lymph node metastasis and a poorer prognosis (Chien et al., 2013).
As a therapeutic target, anti-ALK1 drugs (both in the form of an Fc-fusion protein acting as a soluble receptor for BMP9 and of an anti-ALK1 monoclonal antibody) are under investigation in phase I and phase II clinical trials in a wide range of solid tumours (Vecchia et al., 2013). Phase II studies clinical trials encompass particularly squamous cell carcinoma of the head and neck, endometrial cancer, epithelial ovarian cancer, fallopian tube cancer and primary peritoneal carcinoma for ACE-041 (also known as Dalantercept, the Fc-receptor fusion protein). Dalantercept displayed promising antitumour activity particularly in patients with advanced refractory cancer (Bendell et al., 2014). PF-03446962 (the anti-ALK1 monoclonal antibody), is up to now studied in phase II clinical trials particularly in malignant mesoteliomas of the pleura and transitional cell carcinomas of the bladder. A recent study showed that PF-03446962 has no activity as a single drug in refractory urothelial cancer as is thus suggested, for this kind of cancer, only as a combination therapy with other agents against the VEGF receptor axis (Necchi et al., 2014). Both Dalantercept and PF-03446962 are currently under investigation in phase II trials particularly in advanced and refractory hepatocarcinomas.
As assessed by Hosman et al., 2013, mutations in ACVRL1 gene, as the ones observed in HHT2 patients, seem to reduce the prevalence of some types of solid tumours and account for the unexpected good life expectancy of HHT patients older than 60 years of age. Although it is important to take with care the results of the study due to the methodology used for the assessment (for the statistical and logistic difficulties to perform a longitudinal study in a rare disease, the authors used a questionnaire, inevitably biased), HHT patients older than 60 presented an apparent reduction in lung, liver and colorectal cancer compared to controls. This could potentially be related to the ALK1 haploinsuffiency present in ALK1 HHT mutations, opposite to the overexpression usually showed in cancers. On the other hand, colorectal cancer was instead more frequent in younger HHT patients, particularly in the subgroup with SMAD4 mutations and juvenile polyposis.
  
Entity Hereditary hemorrhagic telangiectasia type 2 (HHT2)
Note Hereditary Hemorrhagic Telangiectasia (HHT), or Rendu-Osler-Weber disease, is a vascular dysplasia inherited as an autosomal dominant trait (Shovlin, 2010; McDonald et al., 2011). It affects approximately 1 in 5-8000 individuals (Faughnan et al., 2011) with regional differences due to founder effects (Westermann et al., 2003, Lesca et al., 2008). The clinical diagnosis of HHT is based on the presence of at least three of the following "Curaçao criteria" (Shovlin et al., 2000): (1) spontaneous, recurrent epistaxis; (2) mucocutaneous telangiectases at characteristic sites as nose, lips, oral cavity, finger tips and gastrointestinal (GI) mucosa; (3) visceral arteriovenous malformations (AVMs) in lungs, liver, GI, brain and spinal cord; (4) family history of first-degree relative in whom HHT has been diagnosed using these criteria. Significant clinical variability was observed in HHT (Lesca et al., 2007; Govani and Shovlin, 2009), with both intra- and interfamilial variations in age-of-onset, localization of lesions, and severity of complications, whereas it usually shows a high penetrance. HHT is usually not apparent at birth, but evolves with age into a recognizable phenotypic pattern. Spontaneous recurrent nosebleeds are the most common and usually earliest clinical manifestation. HHT telangiectases develop and get worse with age. Complete penetrance was found to be by 40 years of age (Porteous et al., 1992). HHT patients show approximately 15-50% of pulmonary AVMs (PAVMs), 32-78% of liver AVMs (HAVMS) and approximately 23% will harbor AVMs in the brain (CAVMs). Although 80% of patients with HHT have gastric or small intestinal telangiectases, only 25-30% of patients will develop symptomatic GI bleeding which usually does not present until the fifth or sixth decades of life (Faughnan et al., 2011).
HHT arises from heterozygous mutations in ENG (HHT1, OMIM #187300) coding for ENDOGLIN (ENG) (McAllister et al., 1994) and ACVRL1 (HHT2, OMIM #600376) coding for ALK1 (Johnson et al., 1996), Type III and Type I TGF-β receptors, respectively. Certain HHT2 patients develop a Pulmonary Artery Hypertension (PAH)-like syndrome, suggesting that ACVRL1 mutations are also likely to be involved in PAH (Trembath et al., 2001; Olivieri et al., 2006). A subset of patients with juvenile polyposis, carrying mutations in SMAD4/MADH4 (JPHT, OMIM #175050), can also develop HHT (Gallione et al., 2004). Recently, mutations in BMP9 were reported in three unrelated families affected by a vascular-anomaly syndrome presenting with phenotypic overlap with HHT (Wooderchak-Donahue et al., 2013). Additional as-yet-unknown HHT genes have been suggested by linkage analysis in two affected kindred on chromosome 5 and on chromosome 7 (Cole et al., 2005; Bayrak-Toydemir et al., 2006). Molecular genetic testing of the three known genes detects mutations in approximately 85% of patients. As reported above, the mutated genes encode proteins that mediate signaling by TGF-β family.
More than 375 ACVRL1 variants are present in the international HHT mutation database and more than 185 are demonstrated to be pathogenic for HHT.
TGF-β ligands regulate angiogenesis through their actions either on endothelial cells (EC) and/or mural cell, demonstrating that they play important roles in both activation (via ALK1) and resolution (via ALK5) phases of angiogenesis. It has been reported that BMP9, rather than BMP10, might be the specific ALK1 ligand and activator of the Smad1/5/8 signaling pathway in endothelial cells and that they are potent inhibitors of EC migration and growth (David et al., 2007). Previous studies have suggested the synergy between Notch and TGF-β, and that Notch signaling modulates the balance between TGF-β/ALK1 and TGF-β/ALK5 signaling pathways (Fu et al., 2009).
  
Entity ALK1-1 and pulmonary arterial hypertension
Note Pulmonary arterial hypertension (PAH) is a severe and rare disease affecting small pulmonary arteries, with progressive remodeling leading to elevated pulmonary vascular resistance and right ventricular failure, and is a major cause of progressive right-sided heart failure and premature death (Trembath et al., 2001). PAH is defined as the sustained elevation of mean pulmonary artery pressure (PA) above 25 mmHg at rest or 30 mmHg during exercise (Rabinovitch, 2012). The histopathology is marked by vascular proliferation/fibrosis, remodeling, and vessel obstruction (Chan and Loscalzo, 2008).
In the second World Symposium held in Evian, France, in 1998, was proposed a clinical classification for pulmonary hypertension. The first category was defined PAH and includes two subgroups, the first incorporates both the idiopathic form (IPAH) that the inherited (HPAH) of the disease. The second subgroup includes a number of conditions associated with various diseases (APAH), including connective tissue diseases, human immunodeficiency virus infection, congenital heart disease, and portal hypertension (Simonneau et al., 2004; Machado et al., 2009).
Heterozygous mutations in the transforming growth factor-β receptor (TGF-β receptor) super family have been genetically linked to PAH and likely play a causative role in the development of disease. Particularly, mutations in the bone morphogenetic factor receptor type 2 (BMPR2) gene account for approximately 70% of all familial pedigrees of PAH (HPAH) and 10-30% of idiopathic PAH cases (IPAH) (Chan and Loscalzo, 2008; Machado et al., 2009).
Much less commonly (5%) two other members of the TGF-β superfamily are also recognized as uncommon causes of PAH: activine A receptor type II-like kinase 1 (ALK1) and, at significant lower frequency, endoglin (ENG) (Harrison et al., 2003). Heterozygous mutations of these genes cause the autosomal dominant vascular disorder hereditary haemorrhagic teleangiectasia (HHT) (Shovlin, 2010). In fact, in a small proportion of HHT patients, was observed a form of pulmonary arterial hypertension that is associated with a model of precapillary pulmonary hypertension that is histopathologically indistinguishable from idiopathic form of PAH. Since the publication by Trembath et al. in 2001 (Trembath et al., 2001), who first reported patients with a mutation in the gene ACVRL1 with clinical features of both PAH and HHT, subsequently, have been recognized several other mutations in the ALK1 gene that seem to predispose patients with HHT development of PAH. This observation was further confirmed by other studies (Olivieri et al., 2006) and extensively discussed by Machado et al. (Machado et al., 2009). The exact prevalence of PAH in the HHT population has not been systematically evaluated, but most authors agree that it is a rare complication found in less than 1% of HHT patients (Cottin et al., 2007). In rare cases, ACVRL1 mutations have been reported to cause IPAH or HPAH without HHT (Harrison et al., 2003).
Both ALK1 and BMPR2 belong to the family of TGF-β receptors, they have different specific ligands but share a common intracellular pathway based on the activation of the SMAD proteins 1/5/8 (Faughnan et al., 2009). The formation of an heteromeric complex with BMPR2 and ALK1 could at least in part explain why any dysregulation of this pathway may promote pulmonary endothelial and/or smooth muscle cell dysfunction and proliferative characteristic of PAH, in subjects carrying mutation either in BMPR2 or in ACVRL1 gene.
Mutations identified in several studies on ALK1 associated with PAH are all likely to disrupt activation of this intracellular pathway and the majority of these comprise missense mutations. Particularly, mutations in exon 10 of ACVRL1 are relevant because they occur in functional domains of the receptor within a conserved carboxyl-terminal region of ALK1 (the non-activating non-down regulating box) NANDOR BOX (Faughnan et al., 2009; Machado et al., 2009). Of note, the NANDOR BOX, located from codon 479 to 489, is necessary for regulation of TGF-β signaling, accordingly any alteration may have effects on TGF-β-induced receptor signaling (Girerd et al., 2010).
Moreover, recent studies in animal models have shown that Alk1 heterozygous mice spontaneously develop signs of pulmonary hypertension in the early months of life, and with increasing age show more occluded vessels and pulmonary vascular remodeling, indicating a progression of the disease. These mice had also higher ROS levels in adult lungs contributing to PAH development compared to control mice. Whereas Bmpr2 heterozygous mouse model requires additional factors, such as hypoxia and serotonin or inflammation, to elicit a pulmonary hypertensive phenotype (Jerkic et al., 2011).
Finally, Girerd B. et al. hypothesized that mutated ACVRL1 status might be associated with distinct PAH phenotypes, as compared with patients PAH without ALK1 mutations. The authors analyzed clinical, functional characteristic, hemodynamic features and outcomes for patients with PAH carrying ACVRL1 mutation. Of notice, these patients were significantly younger at diagnosis (P<0.0001) and death, as compared with patients with PAH without BMPR2 and ACVRL1 mutation. In addition, the carriers of the mutation in ACVRL1 with PAH clinically deteriorated more rapidly and ultimately died of pulmonary hypertension-related causes, indicating that these individuals had more rapid progression, as compare PAH patients without ALK1 mutation, despite similar therapeutic approaches (Girerd et al., 2010).
Pulmonary arterial hypertension is therefore a complex disease that involves the interaction between genetic predisposition and environmental risk factors. The identification of human mutations in components of the TGF-β receptor different from each other but somehow bound by common intracellular signaling pathways, which may lead to the development of pulmonary vascular disease, has provided important targets for further investigation.
  
Entity Hematological malignancies
Note Roughly 80% of non-Hodgkin's lymphomas and 60% of Hodgin lymphomas express ALK1 in their vasculature (Hu-Lowe et al., 2011). The expression of ALK1 in haematological cancers was further confirmed in an exploratory study on patients affected with Acute Myeloid leukemia (AML) (Otten et al., 2011). Using qRT-PCR, ALK1 was demonstrated to be expressed by 82% of patients' samples (pretherapeutic bone marrow or peripheral blood from 93 patients with newly diagnosed AML). Furthermore, formalin-fixed, paraffin-embedded trephine bone marrow specimens from two arbitrarily selected patients with AML and from two patients with non-leukemic reactive changes were analyzed for ALK-1 expressions by immunohistochemistry. Endothelial cells from two AML patients and those with reactive disorders were strongly positive and a fraction of AML blasts stained positively for ALK-1 in AML bone marrows, whereas normal hematopoietic cells were negative.
Anyway, ALK1 alterations, opposite to those in ALK5, seemed not to have a significant impact on survival. Furthermore, the prevalence of haematological cancers in HHT patients as assessed by Hosman et al., 2013 showed no difference compared to controls.
  

External links

Nomenclature
HGNC (Hugo)ACVRL1   175
Cards
AtlasACVRL1ID569ch12q13
Entrez_Gene (NCBI)ACVRL1  94  activin A receptor type II-like 1
GeneCards (Weizmann)ACVRL1
Ensembl (Hinxton)ENSG00000139567 [Gene_View]  chr12:52301202-52317145 [Contig_View]  ACVRL1 [Vega]
ICGC DataPortalENSG00000139567
cBioPortalACVRL1
AceView (NCBI)ACVRL1
Genatlas (Paris)ACVRL1
WikiGenes94
SOURCE (Princeton)NM_000020 NM_001077401
Genomic and cartography
GoldenPath (UCSC)ACVRL1  -  12q13.13   chr12:52301202-52317145 +  12q13.13   [Description]    (hg19-Feb_2009)
EnsemblACVRL1 - 12q13.13 [CytoView]
Mapping of homologs : NCBIACVRL1 [Mapview]
OMIM600376   601284   
Gene and transcription
Genbank (Entrez)AK056725 AK298493 AK300619 AK303331 BC042637
RefSeq transcript (Entrez)NM_000020 NM_001077401
RefSeq genomic (Entrez)AC_000144 NC_000012 NC_018923 NG_009549 NT_029419 NW_001838057 NW_004929384
Consensus coding sequences : CCDS (NCBI)ACVRL1
Cluster EST : UnigeneHs.591026 [ NCBI ]
CGAP (NCI)Hs.591026
Alternative Splicing : Fast-db (Paris)GSHG0006669
Alternative Splicing GalleryENSG00000139567
Gene ExpressionACVRL1 [ NCBI-GEO ]     ACVRL1 [ SEEK ]   ACVRL1 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP37023 (Uniprot)
NextProtP37023  [Medical]
With graphics : InterProP37023
Splice isoforms : SwissVarP37023 (Swissvar)
Catalytic activity : Enzyme2.7.11.30 [ Enzyme-Expasy ]   2.7.11.302.7.11.30 [ IntEnz-EBI ]   2.7.11.30 [ BRENDA ]   2.7.11.30 [ KEGG ]   
Domaine pattern : Prosite (Expaxy)GS (PS51256)    PROTEIN_KINASE_ATP (PS00107)    PROTEIN_KINASE_DOM (PS50011)    PROTEIN_KINASE_ST (PS00108)   
Domains : Interpro (EBI)Activin_rcpt [organisation]   Kinase-like_dom [organisation]   Prot_kinase_dom [organisation]   Protein_kinase_ATP_BS [organisation]   Ser/Thr_kinase_AS [organisation]   TGF_beta_rcpt_GS [organisation]   TGFB_receptor [organisation]  
Related proteins : CluSTrP37023
Domain families : Pfam (Sanger)Activin_recp (PF01064)    Pkinase (PF00069)    TGF_beta_GS (PF08515)   
Domain families : Pfam (NCBI)pfam01064    pfam00069    pfam08515   
Domain families : Smart (EMBL)GS (SM00467)  
DMDM Disease mutations94
Blocks (Seattle)P37023
PDB (SRS)2LCR    3MY0    4FAO   
PDB (PDBSum)2LCR    3MY0    4FAO   
PDB (IMB)2LCR    3MY0    4FAO   
PDB (RSDB)2LCR    3MY0    4FAO   
Human Protein AtlasENSG00000139567 [gene] [tissue] [antibody] [cell] [cancer]
Peptide AtlasP37023
HPRD03181
IPIIPI01013348   IPI01021561   IPI01022365   IPI00784262   
Protein Interaction databases
DIP (DOE-UCLA)P37023
IntAct (EBI)P37023
FunCoupENSG00000139567
BioGRIDACVRL1
InParanoidP37023
Interologous Interaction database P37023
IntegromeDBACVRL1
STRING (EMBL)ACVRL1
Ontologies - Pathways
Ontology : AmiGOangiogenesis  in utero embryonic development  regulation of endothelial cell proliferation  negative regulation of endothelial cell proliferation  positive regulation of endothelial cell proliferation  lymphangiogenesis  blood vessel maturation  blood vessel remodeling  blood vessel endothelial cell proliferation involved in sprouting angiogenesis  protein serine/threonine kinase activity  transmembrane receptor protein serine/threonine kinase activity  receptor signaling protein serine/threonine kinase activity  transforming growth factor beta-activated receptor activity  transforming growth factor beta receptor activity, type I  protein binding  ATP binding  integral component of plasma membrane  regulation of DNA replication  regulation of transcription, DNA-templated  protein phosphorylation  negative regulation of cell adhesion  signal transduction  transforming growth factor beta receptor signaling pathway  blood circulation  regulation of blood pressure  negative regulation of cell proliferation  cell surface  negative regulation of endothelial cell migration  positive regulation of pathway-restricted SMAD protein phosphorylation  activin receptor activity, type I  activin receptor activity, type I  protein kinase binding  signal transduction by phosphorylation  negative regulation of cell growth  negative regulation of cell migration  dendrite  BMP signaling pathway  positive regulation of BMP signaling pathway  positive regulation of chondrocyte differentiation  activin receptor signaling pathway  wound healing, spreading of epidermal cells  neuronal cell body  regulation of blood vessel endothelial cell migration  negative regulation of blood vessel endothelial cell migration  negative regulation of endothelial cell differentiation  positive regulation of endothelial cell differentiation  positive regulation of transcription, DNA-templated  positive regulation of transcription from RNA polymerase II promoter  SMAD binding  metal ion binding  activin binding  transforming growth factor beta binding  protein heterooligomerization  negative regulation of focal adhesion assembly  lymphatic endothelial cell differentiation  artery development  venous blood vessel development  endothelial tube morphogenesis  retina vasculature development in camera-type eye  cellular response to transforming growth factor beta stimulus  cellular response to BMP stimulus  negative regulation of DNA biosynthetic process  
Ontology : EGO-EBIangiogenesis  in utero embryonic development  regulation of endothelial cell proliferation  negative regulation of endothelial cell proliferation  positive regulation of endothelial cell proliferation  lymphangiogenesis  blood vessel maturation  blood vessel remodeling  blood vessel endothelial cell proliferation involved in sprouting angiogenesis  protein serine/threonine kinase activity  transmembrane receptor protein serine/threonine kinase activity  receptor signaling protein serine/threonine kinase activity  transforming growth factor beta-activated receptor activity  transforming growth factor beta receptor activity, type I  protein binding  ATP binding  integral component of plasma membrane  regulation of DNA replication  regulation of transcription, DNA-templated  protein phosphorylation  negative regulation of cell adhesion  signal transduction  transforming growth factor beta receptor signaling pathway  blood circulation  regulation of blood pressure  negative regulation of cell proliferation  cell surface  negative regulation of endothelial cell migration  positive regulation of pathway-restricted SMAD protein phosphorylation  activin receptor activity, type I  activin receptor activity, type I  protein kinase binding  signal transduction by phosphorylation  negative regulation of cell growth  negative regulation of cell migration  dendrite  BMP signaling pathway  positive regulation of BMP signaling pathway  positive regulation of chondrocyte differentiation  activin receptor signaling pathway  wound healing, spreading of epidermal cells  neuronal cell body  regulation of blood vessel endothelial cell migration  negative regulation of blood vessel endothelial cell migration  negative regulation of endothelial cell differentiation  positive regulation of endothelial cell differentiation  positive regulation of transcription, DNA-templated  positive regulation of transcription from RNA polymerase II promoter  SMAD binding  metal ion binding  activin binding  transforming growth factor beta binding  protein heterooligomerization  negative regulation of focal adhesion assembly  lymphatic endothelial cell differentiation  artery development  venous blood vessel development  endothelial tube morphogenesis  retina vasculature development in camera-type eye  cellular response to transforming growth factor beta stimulus  cellular response to BMP stimulus  negative regulation of DNA biosynthetic process  
Protein Interaction DatabaseACVRL1
Wikipedia pathwaysACVRL1
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)ACVRL1
snp3D : Map Gene to Disease94
SNP (GeneSNP Utah)ACVRL1
SNP : HGBaseACVRL1
Genetic variants : HAPMAPACVRL1
Exome VariantACVRL1
1000_GenomesACVRL1 
ICGC programENSG00000139567 
Somatic Mutations in Cancer : COSMICACVRL1 
CONAN: Copy Number AnalysisACVRL1 
Mutations and Diseases : HGMDACVRL1
Mutations and Diseases : intOGenACVRL1
Genomic VariantsACVRL1  ACVRL1 [DGVbeta]
dbVarACVRL1
ClinVarACVRL1
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Diseases
OMIM600376    601284   
MedgenACVRL1
GENETestsACVRL1
Disease Genetic AssociationACVRL1
Huge Navigator ACVRL1 [HugePedia]  ACVRL1 [HugeCancerGEM]
General knowledge
Homologs : HomoloGeneACVRL1
Homology/Alignments : Family Browser (UCSC)ACVRL1
Phylogenetic Trees/Animal Genes : TreeFamACVRL1
Chemical/Protein Interactions : CTD94
Chemical/Pharm GKB GenePA24496
Clinical trialACVRL1
Cancer Resource (Charite)ENSG00000139567
Other databases
Probes
Litterature
PubMed120 Pubmed reference(s) in Entrez
CoreMineACVRL1
iHOPACVRL1
OncoSearchACVRL1

Bibliography

Hereditary haemorrhagic telangiectasia: a clinical analysis.
Porteous ME, Burn J, Proctor SJ.
J Med Genet. 1992 Aug;29(8):527-30.
PMID 1518020
 
Endoglin, a TGF-beta binding protein of endothelial cells, is the gene for hereditary haemorrhagic telangiectasia type 1.
McAllister KA, Grogg KM, Johnson DW, Gallione CJ, Baldwin MA, Jackson CE, Helmbold EA, Markel DS, McKinnon WC, Murrell J, et al.
Nat Genet. 1994 Dec;8(4):345-51.
PMID 7894484
 
Identification of type I receptors for osteogenic protein-1 and bone morphogenetic protein-4.
ten Dijke P, Yamashita H, Sampath TK, Reddi AH, Estevez M, Riddle DL, Ichijo H, Heldin CH, Miyazono K.
J Biol Chem. 1994 Jun 24;269(25):16985-8.
PMID 8006002
 
Mutations in the activin receptor-like kinase 1 gene in hereditary haemorrhagic telangiectasia type 2.
Johnson DW, Berg JN, Baldwin MA, Gallione CJ, Marondel I, Yoon SJ, Stenzel TT, Speer M, Pericak-Vance MA, Diamond A, Guttmacher AE, Jackson CE, Attisano L, Kucherlapati R, Porteous ME, Marchuk DA.
Nat Genet. 1996 Jun;13(2):189-95.
PMID 8640225
 
Mutational analysis of activin/transforming growth factor-beta type I and type II receptor kinases in human pituitary tumors.
D'Abronzo FH, Swearingen B, Klibanski A, Alexander JM.
J Clin Endocrinol Metab. 1999 May;84(5):1716-21.
PMID 10323406
 
Crystal structure of the BMP-2-BRIA ectodomain complex.
Kirsch T, Sebald W, Dreyer MK.
Nat Struct Biol. 2000 Jun;7(6):492-6.
PMID 10881198
 
Diagnostic criteria for hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber syndrome).
Shovlin CL, Guttmacher AE, Buscarini E, Faughnan ME, Hyland RH, Westermann CJ, Kjeldsen AD, Plauchu H.
Am J Med Genet. 2000 Mar 6;91(1):66-7.
PMID 10751092
 
Clinical and molecular genetic features of pulmonary hypertension in patients with hereditary hemorrhagic telangiectasia.
Trembath RC, Thomson JR, Machado RD, Morgan NV, Atkinson C, Winship I, Simonneau G, Galie N, Loyd JE, Humbert M, Nichols WC, Morrell NW, Berg J, Manes A, McGaughran J, Pauciulo M, Wheeler L.
N Engl J Med. 2001 Aug 2;345(5):325-34.
PMID 11484689
 
The BMP7/ActRII extracellular domain complex provides new insights into the cooperative nature of receptor assembly.
Greenwald J, Groppe J, Gray P, Wiater E, Kwiatkowski W, Vale W, Choe S.
Mol Cell. 2003 Mar;11(3):605-17.
PMID 12667445
 
Molecular and functional analysis identifies ALK-1 as the predominant cause of pulmonary hypertension related to hereditary haemorrhagic telangiectasia.
Harrison RE, Flanagan JA, Sankelo M, Abdalla SA, Rowell J, Machado RD, Elliott CG, Robbins IM, Olschewski H, McLaughlin V, Gruenig E, Kermeen F, Halme M, Raisanen-Sokolowski A, Laitinen T, Morrell NW, Trembath RC.
J Med Genet. 2003 Dec;40(12):865-71.
PMID 14684682
 
Structures of an ActRIIB:activin A complex reveal a novel binding mode for TGF-beta ligand:receptor interactions.
Thompson TB, Woodruff TK, Jardetzky TS.
EMBO J. 2003 Apr 1;22(7):1555-66.
PMID 12660162
 
The prevalence and manifestations of hereditary hemorrhagic telangiectasia in the Afro-Caribbean population of the Netherlands Antilles: a family screening.
Westermann CJ, Rosina AF, De Vries V, de Coteau PA.
Am J Med Genet A. 2003 Feb 1;116A(4):324-8.
PMID 12522784
 
A combined syndrome of juvenile polyposis and hereditary haemorrhagic telangiectasia associated with mutations in MADH4 (SMAD4).
Gallione CJ, Repetto GM, Legius E, Rustgi AK, Schelley SL, Tejpar S, Mitchell G, Drouin E, Westermann CJ, Marchuk DA.
Lancet. 2004 Mar 13;363(9412):852-9.
PMID 15031030
 
Clinical classification of pulmonary hypertension.
Simonneau G, Galie N, Rubin LJ, Langleben D, Seeger W, Domenighetti G, Gibbs S, Lebrec D, Speich R, Beghetti M, Rich S, Fishman A.
J Am Coll Cardiol. 2004 Jun 16;43(12 Suppl S):5S-12S. (REVIEW)
PMID 15194173
 
A new locus for hereditary haemorrhagic telangiectasia (HHT3) maps to chromosome 5.
Cole SG, Begbie ME, Wallace GM, Shovlin CL.
J Med Genet. 2005 Jul;42(7):577-82.
PMID 15994879
 
A fourth locus for hereditary hemorrhagic telangiectasia maps to chromosome 7.
Bayrak-Toydemir P, McDonald J, Akarsu N, Toydemir RM, Calderon F, Tuncali T, Tang W, Miller F, Mao R.
Am J Med Genet A. 2006 Oct 15;140(20):2155-62.
PMID 16969873
 
Echocardiographic screening discloses increased values of pulmonary artery systolic pressure in 9 of 68 unselected patients affected with hereditary hemorrhagic telangiectasia.
Olivieri C, Lanzarini L, Pagella F, Semino L, Corno S, Valacca C, Plauchu H, Lesca G, Barthelet M, Buscarini E, Danesino C.
Genet Med. 2006 Mar;8(3):183-90.
PMID 16540754
 
Pulmonary vascular manifestations of hereditary hemorrhagic telangiectasia (rendu-osler disease).
Cottin V, Dupuis-Girod S, Lesca G, Cordier JF.
Respiration. 2007;74(4):361-78. (REVIEW)
PMID 17641482
 
Identification of BMP9 and BMP10 as functional activators of the orphan activin receptor-like kinase 1 (ALK1) in endothelial cells.
David L, Mallet C, Mazerbourg S, Feige JJ, Bailly S.
Blood. 2007 Mar 1;109(5):1953-61. Epub 2006 Oct 26.
PMID 17068149
 
Genotype-phenotype correlations in hereditary hemorrhagic telangiectasia: data from the French-Italian HHT network.
Lesca G, Olivieri C, Burnichon N, Pagella F, Carette MF, Gilbert-Dussardier B, Goizet C, Roume J, Rabilloud M, Saurin JC, Cottin V, Honnorat J, Coulet F, Giraud S, Calender A, Danesino C, Buscarini E, Plauchu H; French-Italian-Rendu-Osler Network.
Genet Med. 2007 Jan;9(1):14-22.
PMID 17224686
 
Antitumor activity of ALK1 in pancreatic carcinoma cells.
Ungefroren H, Schniewind B, Groth S, Chen WB, Muerkoster SS, Kalthoff H, Fandrich F.
Int J Cancer. 2007 Apr 15;120(8):1641-51.
PMID 17230504
 
Pathogenic mechanisms of pulmonary arterial hypertension.
Chan SY, Loscalzo J.
J Mol Cell Cardiol. 2008 Jan;44(1):14-30. Epub 2007 Sep 20. (REVIEW)
PMID 17950310
 
Hereditary hemorrhagic telangiectasia: evidence for regional founder effects of ACVRL1 mutations in French and Italian patients.
Lesca G, Genin E, Blachier C, Olivieri C, Coulet F, Brunet G, Dupuis-Girod S, Buscarini E, Soubrier F, Calender A, Danesino C, Giraud S, Plauchu H; French-Italian HHT Network.
Eur J Hum Genet. 2008 Jun;16(6):742-9. doi: 10.1038/ejhg.2008.3. Epub 2008 Feb 20.
PMID 18285823
 
The pulmonary vascular complications of hereditary haemorrhagic telangiectasia.
Faughnan ME, Granton JT, Young LH.
Eur Respir J. 2009 May;33(5):1186-94. doi: 10.1183/09031936.00061308. (REVIEW)
PMID 19407052
 
Differential regulation of transforming growth factor beta signaling pathways by Notch in human endothelial cells.
Fu Y, Chang A, Chang L, Niessen K, Eapen S, Setiadi A, Karsan A.
J Biol Chem. 2009 Jul 17;284(29):19452-62. doi: 10.1074/jbc.M109.011833. Epub 2009 May 27.
PMID 19473993
 
Hereditary haemorrhagic telangiectasia: a clinical and scientific review.
Govani FS, Shovlin CL.
Eur J Hum Genet. 2009 Jul;17(7):860-71. doi: 10.1038/ejhg.2009.35. Epub 2009 Apr 1. (REVIEW)
PMID 19337313
 
Genetics and genomics of pulmonary arterial hypertension.
Machado RD, Eickelberg O, Elliott CG, Geraci MW, Hanaoka M, Loyd JE, Newman JH, Phillips JA 3rd, Soubrier F, Trembath RC, Chung WK.
J Am Coll Cardiol. 2009 Jun 30;54(1 Suppl):S32-42. doi: 10.1016/j.jacc.2009.04.015. (REVIEW)
PMID 19555857
 
Characterization of the human Activin-A receptor type II-like kinase 1 (ACVRL1) promoter and its regulation by Sp1.
Garrido-Martin EM, Blanco FJ, Fernandez-L A, Langa C, Vary CP, Lee UE, Friedman SL, Botella LM, Bernabeu C.
BMC Mol Biol. 2010 Jun 29;11:51. doi: 10.1186/1471-2199-11-51.
PMID 20587022
 
Clinical outcomes of pulmonary arterial hypertension in patients carrying an ACVRL1 (ALK1) mutation.
Girerd B, Montani D, Coulet F, Sztrymf B, Yaici A, Jais X, Tregouet D, Reis A, Drouin-Garraud V, Fraisse A, Sitbon O, O'Callaghan DS, Simonneau G, Soubrier F, Humbert M.
Am J Respir Crit Care Med. 2010 Apr 15;181(8):851-61. doi: 10.1164/rccm.200908-1284OC. Epub 2010 Jan 7.
PMID 20056902
 
Hereditary haemorrhagic telangiectasia: pathophysiology, diagnosis and treatment.
Shovlin CL.
Blood Rev. 2010 Nov;24(6):203-19. doi: 10.1016/j.blre.2010.07.001. Epub 2010 Sep 25. (REVIEW)
PMID 20870325
 
International guidelines for the diagnosis and management of hereditary haemorrhagic telangiectasia.
Faughnan ME, Palda VA, Garcia-Tsao G, Geisthoff UW, McDonald J, Proctor DD, Spears J, Brown DH, Buscarini E, Chesnutt MS, Cottin V, Ganguly A, Gossage JR, Guttmacher AE, Hyland RH, Kennedy SJ, Korzenik J, Mager JJ, Ozanne AP, Piccirillo JF, Picus D, Plauchu H, Porteous ME, Pyeritz RE, Ross DA, Sabba C, Swanson K, Terry P, Wallace MC, Westermann CJ, White RI, Young LH, Zarrabeitia R; HHT Foundation International - Guidelines Working Group.
J Med Genet. 2011 Feb;48(2):73-87. doi: 10.1136/jmg.2009.069013. Epub 2009 Jun 23.
PMID 19553198
 
Targeting activin receptor-like kinase 1 inhibits angiogenesis and tumorigenesis through a mechanism of action complementary to anti-VEGF therapies.
Hu-Lowe DD, Chen E, Zhang L, Watson KD, Mancuso P, Lappin P, Wickman G, Chen JH, Wang J, Jiang X, Amundson K, Simon R, Erbersdobler A, Bergqvist S, Feng Z, Swanson TA, Simmons BH, Lippincott J, Casperson GF, Levin WJ, Stampino CG, Shalinsky DR, Ferrara KW, Fiedler W, Bertolini F.
Cancer Res. 2011 Feb 15;71(4):1362-73. doi: 10.1158/0008-5472.CAN-10-1451. Epub 2011 Jan 6.
PMID 21212415
 
Pulmonary hypertension in adult Alk1 heterozygous mice due to oxidative stress.
Jerkic M, Kabir MG, Davies A, Yu LX, McIntyre BA, Husain NW, Enomoto M, Sotov V, Husain M, Henkelman M, Belik J, Letarte M.
Cardiovasc Res. 2011 Dec 1;92(3):375-84. doi: 10.1093/cvr/cvr232. Epub 2011 Aug 22.
PMID 21859819
 
Hereditary hemorrhagic telangiectasia: an overview of diagnosis, management, and pathogenesis.
McDonald J, Bayrak-Toydemir P, Pyeritz RE.
Genet Med. 2011 Jul;13(7):607-16. doi: 10.1097/GIM.0b013e3182136d32. (REVIEW)
PMID 21546842
 
Expression of TGF-β receptor ALK-5 has a negative impact on outcome of patients with acute myeloid leukemia.
Otten J, Schmitz L, Vettorazzi E, Schultze A, Marx AH, Simon R, Krauter J, Loges S, Sauter G, Bokemeyer C, Fiedler W.
Leukemia. 2011 Feb;25(2):375-9. doi: 10.1038/leu.2010.273. Epub 2010 Nov 23.
PMID 21304536
 
ACVRL1 germinal mosaic with two mutant alleles in hereditary hemorrhagic telangiectasia associated with pulmonary arterial hypertension.
Eyries M, Coulet F, Girerd B, Montani D, Humbert M, Lacombe P, Chinet T, Gouya L, Roume J, Axford MM, Pearson CE, Soubrier F.
Clin Genet. 2012 Aug;82(2):173-9. doi: 10.1111/j.1399-0004.2011.01727.x. Epub 2011 Jul 13.
PMID 21651515
 
Molecular pathogenesis of pulmonary arterial hypertension.
Rabinovitch M.
J Clin Invest. 2012 Dec 3;122(12):4306-13. doi: 10.1172/JCI60658. Epub 2012 Dec 3. (REVIEW)
PMID 23202738
 
Specificity and structure of a high affinity activin receptor-like kinase 1 (ALK1) signaling complex.
Townson SA, Martinez-Hackert E, Greppi C, Lowden P, Sako D, Liu J, Ucran JA, Liharska K, Underwood KW, Seehra J, Kumar R, Grinberg AV.
J Biol Chem. 2012 Aug 10;287(33):27313-25. doi: 10.1074/jbc.M112.377960. Epub 2012 Jun 20.
PMID 22718755
 
Evaluation of the prognostic value of TGF-β superfamily type I receptor and TGF-β type II receptor expression in nasopharyngeal carcinoma using high-throughput tissue microarrays.
Zhang W, Zeng Z, Fan S, Wang J, Yang J, Zhou Y, Li X, Huang D, Liang F, Wu M, Tang K, Cao L, Li X, Xiong W, Li G.
J Mol Histol. 2012 Jun;43(3):297-306. doi: 10.1007/s10735-012-9392-4. Epub 2012 Mar 6.
PMID 22391627
 
The expression of activin receptor-like kinase 1 among patients with head and neck cancer.
Chien CY, Chuang HC, Chen CH, Fang FM, Chen WC, Huang CC, Huang HY.
Otolaryngol Head Neck Surg. 2013 Jun;148(6):965-73. doi: 10.1177/0194599813479556. Epub 2013 Feb 27.
PMID 23447486
 
Specific cancer rates may differ in patients with hereditary haemorrhagic telangiectasia compared to controls.
Hosman AE, Devlin HL, Silva BM, Shovlin CL.
Orphanet J Rare Dis. 2013 Dec 20;8:195. doi: 10.1186/1750-1172-8-195.
PMID 24354965
 
Papillary thyroid carcinoma with bone formation.
Na KY, Kim HS, Lee SK, Jung WW, Sung JY, Kim YW, Park YK.
Pathol Res Pract. 2013 Jan 15;209(1):14-8. doi: 10.1016/j.prp.2012.10.001. Epub 2012 Nov 21.
PMID 23177617
 
NANOG promotes liver cancer cell invasion by inducing epithelial-mesenchymal transition through NODAL/SMAD3 signaling pathway.
Sun C, Sun L, Jiang K, Gao DM, Kang XN, Wang C, Zhang S, Huang S, Qin X, Li Y, Liu YK.
Int J Biochem Cell Biol. 2013 Jun;45(6):1099-108. doi: 10.1016/j.biocel.2013.02.017. Epub 2013 Mar 7.
PMID 23474366
 
Activin Receptor-like kinase 1: a novel anti-angiogenesis target from TGF-β family.
Vecchia L, Olivieri C, Scotti C.
Mini Rev Med Chem. 2013 Aug;13(10):1398-406.
PMID 23815578
 
BMP9 mutations cause a vascular-anomaly syndrome with phenotypic overlap with hereditary hemorrhagic telangiectasia.
Wooderchak-Donahue WL, McDonald J, O'Fallon B, Upton PD, Li W, Roman BL, Young S, Plant P, Fulop GT, Langa C, Morrell NW, Botella LM, Bernabeu C, Stevenson DA, Runo JR, Bayrak-Toydemir P.
Am J Hum Genet. 2013 Sep 5;93(3):530-7. doi: 10.1016/j.ajhg.2013.07.004. Epub 2013 Aug 22.
PMID 23972370
 
Safety, pharmacokinetics, pharmacodynamics, and antitumor activity of dalantercept, an activin receptor-like kinase-1 ligand trap, in patients with advanced cancer.
Bendell JC, Gordon MS, Hurwitz HI, Jones SF, Mendelson DS, Blobe GC, Agarwal N, Condon CH, Wilson D, Pearsall AE, Yang Y, McClure T, Attie KM, Sherman ML, Sharma S.
Clin Cancer Res. 2014 Jan 15;20(2):480-9. doi: 10.1158/1078-0432.CCR-13-1840. Epub 2013 Oct 30.
PMID 24173543
 
PF-03446962, a fully-human monoclonal antibody against transforming growth-factor β (TGFβ) receptor ALK1, in pre-treated patients with urothelial cancer: an open label, single-group, phase 2 trial.
Necchi A, Giannatempo P, Mariani L, Fare E, Raggi D, Pennati M, Zaffaroni N, Crippa F, Marchiano A, Nicolai N, Maffezzini M, Togliardi E, Daidone MG, Gianni AM, Salvioni R, De Braud F.
Invest New Drugs. 2014 Jun;32(3):555-60. doi: 10.1007/s10637-014-0074-9. Epub 2014 Feb 26.
PMID 24566706
 
Canonical Wnt signaling skews TGF-β signaling in chondrocytes towards signaling via ALK1 and Smad 1/5/8.
van den Bosch MH, Blom AB, van Lent PL, van Beuningen HM, Blaney Davidson EN, van der Kraan PM, van den Berg WB.
Cell Signal. 2014 May;26(5):951-8. doi: 10.1016/j.cellsig.2014.01.021. Epub 2014 Jan 23.
PMID 24463008
 
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Written03-2014Federica Ornati, Luca Vecchia, Claudia Scotti, Sara Plumitallo, Carla Olivieri
Dept of Molecular Medicine, Unit of General Biology and Medical Genetics, University of Pavia, Italy (FO, SP, CO); Dept of Molecular Medicine, Unit of Immunology and General Pathology, University of Pavia, Italy (LV, CS)

Citation

This paper should be referenced as such :
Ornati F, Vecchia L, Scotti C, Plumitallo S, Olivieri C
ACVRL1 (activin A receptor type II-like 1);
Atlas Genet Cytogenet Oncol Haematol. March 2014
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/ACVRL1ID569ch12q13.html

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