Disease relevance of Acvr1

• Our results show that mice lacking Alk2 in the neural crest display multiple craniofacial defects including cleft palate and a hypotrophic mandible [1].
• Testicular germ cell tumours of adolescents and adults (TGCTs) and spermatocytic seminomas expressed activin type I and type II receptors (ActRI and ActRII respectively) [2].
• Two cell lines, SKR1 and NKK1, were established from renal cell carcinomas (RCC) with different histopathologic characteristics: SKR1 from grade 3, solid type, pleomorphic cell type carcinoma in a 66-year-old male and NKK1 from grade 2, alveolar type, clear cell carcinoma in a 49-year-old female [3].

High impact information on Acvr1

• Secondly, Alk2-deficient embryos completely lacked PGCs and the heterozygotes had reduced numbers, resembling Bmp4-deficient phenotypes [4].
• BMP signaling mediated by ALK2 in the visceral endoderm is necessary for the generation of primordial germ cells in the mouse embryo [4].
• Our results also implicate the Tsk7L type I receptor as mediating the TGF-beta-induced epithelial to mesenchymal transition [5].
• The positions of introns in the intracellular domain are almost identical to those of the mouse serine-threonine kinase receptor TSK-7L [6].
• These results suggest that Smad7 selectively interferes with the ActR-I pathway in activin signal transduction [7].

Biological context of Acvr1

• Thirdly, expression of constitutively active ALK2 in the VE, but not in the epiblast, was sufficient to rescue the PGC phenotype in Bmp4-deficient embryos [4].
• BMP type I receptor ALK2 is essential for proper patterning at late gastrulation during mouse embryogenesis [8].
• Furthermore, dominant-negative and antisense strategies showed that ALK2 is essential for MIS-induced signaling in two independent assays, the cellular Tlx-2 reporter gene assay and the Müllerian duct regression organ culture assay [9].
• Collectively, these results indicate that the BMP type I receptor ALK2 in endothelial cells plays a critical non-redundant role in early phases of endocardial cushion formation during cardiac morphogenesis [10].
• The mouse ActRIA gene is encoded by 10 exons and spans approximately 40 kb [11].

Anatomical context of Acvr1

• In contrast, osteopontin (Spp1) transcript levels in activated microglia were not reduced by Acvr1 signalling [12].
• Thus, ALK-2 and ALK-3 (or ALK-6) might synergistically induce osteoblast differentiation of C2C12 cells, possibly through efficient activation of downstream signaling pathways [13].
• To determine in which germ layer ActRIA functions during gastrulation, we performed reciprocal chimera analyses [14].
• Expression analyses revealed that ALK2 is present in all MIS target tissues including the mesenchyme surrounding the epithelial Müllerian duct [9].
• Craniofacial defects in mice lacking BMP type I receptor Alk2 in neural crest cells [1].

Associations of Acvr1 with chemical compounds

• The type I serine/threonine kinase receptor ActRIA (ALK2) is required for gastrulation of the mouse embryo [14].
• NKK1 was about 20 times more resistant to doxorubicin and vinblastine as compared to SKR1 [3].

Physical interactions of Acvr1

• Here we report that Alk8 also forms active signaling complexes with TGF-beta in the presence of TGF-betaRII [15].

Regulatory relationships of Acvr1

• Notably, activated Acvr1 signalling gave significantly lower TBI-induced up-regulations of Gfap and Phox2a mRNA levels, indicating reductions in astroglial and neuronal reactions to injury [12].

Other interactions of Acvr1

• By contrast, ALK-2 and ALK-3 immunostainings in E14 were barely detectable [16].
• The serine/threonine transmembrane receptor ALK2 mediates Müllerian inhibiting substance signaling [9].
• Collectively, we conclude that MIS employs a bone morphogenetic protein-like signaling pathway and uses ALK2 as its type I receptor [9].
• Type I receptors (Alk2, Alk3 and Alk6) are the primary determinants of signaling specificity and therefore understanding their function is important in revealing the developmental roles of molecular pathways regulated by BMPs [1].
• Moreover, in Alk2 mutants, the distal outflow tract fails to express Msx1, one of the major effectors of BMP signaling [17].

Analytical, diagnostic and therapeutic context of Acvr1

• To elucidate its function in mouse development, we disrupted the transmembrane domain of ActRIA by gene targeting [14].
• We examined the level of ActR-I protein during mouse development by immunohistochemistry [18].
• We studied the distribution of ActR-I and ActR-IB mRNAs in postimplantation mouse embryos by in situ hybridization [19].
• Both SKR1 and NKK1 induced tumors at the site of subcutaneous injection of nude mice [3].

References