Recombinant Human alk5 Protein (aa 200-503, His & GST Tag)

Name: Recombinant Human alk5 Protein (aa 200-503, His & GST Tag)
Brand: Beta LifeScience
SKU: BLPSN-0146
Availability: InStock

Collections: Enzymes, Kinase, Recombinant proteins

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Product Overview

Tag	His&GST
Host Species	Human
Accession	P36897
Synonym	AAT5, ACVRLK4, ALK-5, ALK5, ESS1, LDS1, LDS1A, LDS2A, MSSE, SKR4, tbetaR-I, TGFR-1
Background	Transforming growth factor, beta receptor I, also known as Transforming growth factor-beta receptor type I , Serine / threonine-protein kinase receptor R4, Activin receptor-like kinase 5, SKR4, ALK-5, and TGFBR1, is a single-pass type I membrane protein which belongs to the protein kinase superfamily and TGFB receptor subfamily. TGFBR1 / ALK-5 is found in all tissues examined. It is most abundant in placenta and least abundant in brain and heart. TGF-beta functions as a tumor suppressor by inhibiting the cell cycle in the G1 phase. Administration of TGF-beta is able to protect against mammary tumor development in transgenic mouse models in vivo. Disruption of the TGF-beta/SMAD pathway has been implicated in a variety of human cancers, with the majority of colon and gastric cancers being caused by an inactivating mutation of TGF-beta RII. On ligand binding, TGFBR1 / ALK-5 forms a receptor complex consisting of two type I I and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which auto-phosphorylate, then bind and activate SMAD transcriptional regulators. TGF-beta signaling via TGFBR1 / ALK-5 is not required in myocardial cells during mammalian cardiac development, but plays an irreplaceable cell-autonomous role regulating cellular communication, differentiation and proliferation in endocardial and epicardial cells. Defects in TGFBR1 / ALK-5 are the cause of Loeys-Dietz syndrome type 1A (LDS1A), Loeys-Dietz syndrome type 2A (LDS2A), and aortic aneurysm familial thoracic type 5 (AAT5).
Description	A DNA sequence encoding the human ALK5 (P36897-1) (Thr200-Mey503) was fused with the N-terminal His-tagged GST tag at the N-terminus.
Source	Baculovirus-Insect Cells
Predicted N Terminal	Met
AA Sequence	Thr200-Mey503
Molecular Weight	The recombinant human ALK5/GST chimera consists of 541 a.a. and has a calculated molecular mass of 62.6 kDa. The recombinant protein migrates approximately 57 kDa band in SDS-PAGE under reducing conditions.
Purity	>95% as determined by SDS-PAGE
Endotoxin	< 1.0 EU per μg of the protein as determined by the LAL method
Bioactivity	The specific activity was determined to be > 10 nmol/min/mg using casein as substrate.
Formulation	Supplied as sterile 20mM Tris, 500mM Nacl, pH 8.5, 10% glycerol.
Stability	The recombinant proteins are stable for up to 1 year from date of receipt at -70°C.
Usage	For Research Use Only
Storage	Store the protein under sterile conditions at -20°C to -80°C. It is recommended that the protein be aliquoted for optimal storage. Avoid repeated freeze-thaw cycles.

Target Details

Target Function	Transmembrane serine/threonine kinase forming with the TGF-beta type II serine/threonine kinase receptor, TGFBR2, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. Transduces the TGFB1, TGFB2 and TGFB3 signal from the cell surface to the cytoplasm and is thus regulating a plethora of physiological and pathological processes including cell cycle arrest in epithelial and hematopoietic cells, control of mesenchymal cell proliferation and differentiation, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. The formation of the receptor complex composed of 2 TGFBR1 and 2 TGFBR2 molecules symmetrically bound to the cytokine dimer results in the phosphorylation and the activation of TGFBR1 by the constitutively active TGFBR2. Activated TGFBR1 phosphorylates SMAD2 which dissociates from the receptor and interacts with SMAD4. The SMAD2-SMAD4 complex is subsequently translocated to the nucleus where it modulates the transcription of the TGF-beta-regulated genes. This constitutes the canonical SMAD-dependent TGF-beta signaling cascade. Also involved in non-canonical, SMAD-independent TGF-beta signaling pathways. For instance, TGFBR1 induces TRAF6 autoubiquitination which in turn results in MAP3K7 ubiquitination and activation to trigger apoptosis. Also regulates epithelial to mesenchymal transition through a SMAD-independent signaling pathway through PARD6A phosphorylation and activation.
Subcellular Location	Cell membrane; Single-pass type I membrane protein. Cell junction, tight junction. Cell surface. Membrane raft.
Protein Families	Protein kinase superfamily, TKL Ser/Thr protein kinase family, TGFB receptor subfamily
Database References	HGNC: 11772 OMIM: 132800 KEGG: hsa:7046 STRING: 9606.ENSP00000364133 UniGene: Hs.494622
Associated Diseases	Loeys-Dietz syndrome 1 (LDS1); Multiple self-healing squamous epithelioma (MSSE)
Tissue Specificity	Found in all tissues examined, most abundant in placenta and least abundant in brain and heart. Expressed in a variety of cancer cell lines.

Gene Functions References

GPR50 is a TbetaRI co-receptor with potential impact on cancer development PMID: 29572483
Systemic activation of Activin A signaling causes chronic kidney disease-mineral bone disorder. (Review) PMID: 30142896
TGFbetaR1 rs10739778 was associated with blood pressure in healthy pregnant women. PMID: 29183791
Treatment of T. cruzi-infected cardiac spheroids with SB 431542, a selective inhibitor of TGF-b type I receptor, resulted in a reduction in the size of spheroids, which was accompanied by a decrease in parasite load and in fibronectin expression. PMID: 29208458
TGFBR1/2 genetic variants (in particular when evaluated as a burden by score) might play a role in modulating the severity of cardiovascular manifestation in Marfan syndrome. PMID: 28847661
Findings provide evidence that TGFBR-1 expression is regulated by SLC35F2 which exerts its oncogenic effect on papillary thyroid carcinoma progression through activation of TGFBR-1 and ASK-1. PMID: 29274137
rs334348 polymorphism may influence individual's susceptibility to endometriosis and its severity PMID: 28277133
miR-130a-3p might play a critical role in negatively regulating hepatic stellate cell activation and proliferation in the progression of nonalcoholic fibrosing steatohepatitis by directly targeting TGFBR1 and TGFBR2 via the TGF-beta/SMAD signaling pathway. PMID: 28518142
TGFbetaR1 signaling was involved in 14-3-3zeta-mediated cell proliferation and metastasis of lung squamous cell carcinoma cells. PMID: 27764818
Mutational activation of BRAF confers sensitivity to TGFBR1 inhibitors in human melanoma cells. PMID: 27835901
Loeys-Dietz syndrome patients with confirmed mutations in TGFBR1 or TGFBR2 had an increased prevalence of inflammatory bowel disease PMID: 27508510
ALK5 is an important mediator of HTFs fibrosis. ALK5 is a potential therapeutic target to suppress scar formation after filtration surgery. PMID: 28632033
PAR2 is crucial for TGF-beta1-induced cell motility by its ability to sustain expression of ALK5. Therapeutically targeting PAR2 may thus be a promising approach in preventing TGF-beta-dependent driven metastatic dissemination in PDAC and possibly other stroma-rich tumour types. PMID: 27248167
Data show that twist-related protein 1 (Twist1) requires TGF-beta type-I receptor (TGFBR1)-activation for activation for epithelial-mesenchymal transition (EMT)-induction. PMID: 27105506
combined inhibition of ALK5 and CTGF is required to prevent TGFbeta-induced nodule formation in tri-cellular cultures PMID: 28815607
Aortic diseases in patients with TGFBR1 or TGFBR2 mutations show the same prevalence of systemic features and the same global survival. PMID: 27879313
In this small cohort, the results did not reach significance to identify the TFGBR1*6A allele as a major modifier for aortic dilation, ectopia lentis, or systemic features associated with MFS or other connective tissue disorders. PMID: 27112580
Results show that TGFBR1 expression is regulated in bladder cancer cell through its desumoylation by SENP2. PMID: 28574613
Low TGFBR1 expression is associated with oral cancer progression. PMID: 28146434
TGF-beta type I, II, and III receptors were all identified in pregnant serum; all were substantially elevated in early-onset but not late-onset preeclampsia. Endoglin was increased in both subtypes. PMID: 28633389
Overexpression of truncated ALK5 in a B-cell line counteracted BMP-7-induced apoptosis, whereas overexpression of truncated ALK4 had no effect. PMID: 28489883
Although TGFbeta1/2 receptors are downregulated in breast cancer, their expression in tumors is an indicator of aggressive breast cancer phenotype. PMID: 27445263
Higher proportions of early-onset Diffuse Gastric Cancers (DGCs) contained somatic mutations in CDH1 or TGFBR1 compared with late-onset DGCs. A smaller proportion of early-onset DGCs contained somatic mutations in RHOA. CDH1 alterations, but not RHOA mutations, were associated with shorter survival times. Female predominance in early-onset DGC may be related to relatively high rates of somatic CDH1 and TGFBR1 mutations. PMID: 28522256
Coronin 1B constitutively binds to TGF beta receptor I in vascular smooth muscle cells. PMID: 28625921
BIX02189 is a potent inhibitor of TGF-beta type I receptor that can block the lung tumor metastatic activity of TGF-beta1. PMID: 27543359
In luciferase assays, the risk-associated allele for rs868 was associated with half the luciferase expression in the presence of miRNA let-7b-5p compared with protective allele, suggesting more binding of let-7b-5p and less TGFBR1 expression. Thus, rs868 potentially is acolorectal ca CRC risk-causing allele. Our results support the concept that rs868 is associated with lower TGFBR1 expression thereby increasing CRC risk. PMID: 27234654
Data show that signal transducing adaptor proteins APPL1 and APPL2 are required for TGFbeta-induced nuclear translocation of TGFbeta type I receptor (TbetaRI)-ICD and for cancer cell invasiveness of prostate and breast cancer cell lines. PMID: 26583432
Evidence supporting a genetic basis includes the autosomal dominance of Bicuspid aortic valve inheritance patterns, and the identification of mutations in transforming growth factor beta receptor 1. PMID: 26766164
This work details a novel mechanism by which cellular tension regulates TGFbeta receptor organization, multimerization, and function. PMID: 26652004
miR-181b functions as a tumor suppressor and has an important role in proliferation, chemosensitivity to DDP and metastasis of NSCLC by targeting TGFbetaR1/Smad signaling pathway. PMID: 26620926
Protease activated receptor-1 mediated dual kinase receptor transactivation stimulates the expression of glycosaminoglycan synthesizing genes and transforming growth factor beta receptor 1 PMID: 26548632
Studies indicate that the transforming growth factor beta receptor I 6A (TbetaR-I 6A) allele was associated with breast cancer risk. PMID: 26616150
Women who carry the TGFBR1*6A allele are at lower risk of developing breast cancer. PMID: 26165686
Data suggest that transient suppression of TGFbeta receptor I (TGFbeta receptor) signaling may improve the outcome of islet transplantation. PMID: 26872091
Blocking TGFBR1 receptor up-regulated p21 expression while inhibiting breast tumor cell growth. PMID: 26187313
Short hairpin-mediated downregulation of either ALK5 or ALK1 resulted in a strong inhibition of TGFbeta-induced chondrogenesis. PMID: 26720610
MiR-1343 reduces the expression of both TGF-beta receptor 1 and 2 by directly targeting their 3'-UTRs. PMID: 26542979
these findings demonstrate that syntenin may act as an important positive regulator of TGF-b signaling by regulating caveolin-1-mediated internalization of TbRI; thus, providing a novel function for syntenin that is linked to cancer progression PMID: 25893292
Int7G24A polymorphism of gene TGFBR1 involved in the TGF-beta signaling pathway had a significantly increased risk for cancer development. (Meta-analysis) PMID: 26074400
Data show that macitentan interferes with the profibrotic action of transforming growth factor-beta (TGF-beta), blocking the endothelin receptor type A (ET-1 receptor) portion of the ET-1/TGF-beta receptor complex. PMID: 26357964
Treatment with a TGFBR1 kinase inhibitor, endocytosis inhibitors or a lysosome inhibitor, normalized the levels of TGFBR1 and TGFBR2. PMID: 25882708
we showed significantly higher HDAC6 levels in GBM from the patients and further showed evidence supporting TGFbeta receptor signaling pathway as a downstream target of HDAC6 in glioblastoma multiforme PMID: 26150340
results indicate the critical role of TGF-beta R1/Smad2/3 signaling in carbon nanotube-induced fibrogenesis by upregulating collagen production in lung fibroblasts PMID: 26472812
The direct fusion of clathrin-coated and caveolae vesicles during TGF-beta receptor endocytic trafficking, which leads to the formation of the multifunctional sorting device, caveolin-1-positive early endosomes, for TGF-beta receptors. PMID: 25998683
Data show that tacrolimus-induced NAD(P)H-oxidase 4 (Nox4) expression in by aberrant TGF-beta receptor signalling. PMID: 24816588
a case-control study and systematic literature review found that sporadic, but not familial colorectal cancer, was associated with TGFBR1*6A polymorphism. PMID: 24880985
Chinese Han family a pathogenic mutation (rs111426349, c.1459C >T) (TGFBR1) of familial thoracic aortic aneurysm was confirmed, which result in the amino acid substitution p.R487W. PMID: 25110237
TGFBR1 mutations in patients with dural ectasia in Loeys-Dietz syndrome PMID: 24344637
Donor rs868 AA genotype was associated with worse clinical course of recurrent hepatitis C and more severe symptoms of hepatitis C and fibrosis during follow-up after liver transplantation. PMID: 25502482
Characteristic TGFbetaR1 expression pattern in keratoacanthoma can facilitate histopathologic distinction from squamous cell carcinoma. PMID: 24954139

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