Database for Annotation, Visualization and Integrated Discovery 2.1
National Institute of Allergy and Infectious Disease
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SMAD family member 2(SMAD2) SMAD family member 2(SMAD2) Related Genes Homo sapiens
CYTOBAND 18q21.1,
GENERIF_SUMMARY Crystal structure of a phosphorylated Smad2. Recognition of phosphoserine by the MH2 domain and insights on Smad function in TGF-beta signaling, repression of transactivating activity by association with a novel splice variant of CCAAT-binding factor C subunit, c-Jun associates with the oncoprotein Ski and suppresses Smad2 transcriptional activity, activation by transforming growth factor beta in absence of receptor endocytosis, HTLV-1 tax represses Smad-mediated TGF-beta signaling., activation of TGF-beta1/Smad2 signaling is associated with airway remodeling in asthma, Nucleocytoplasmic shuttling of Smads 2, 3, and 4 permits sensing of TGF-beta receptor activity., overexpression of adenoviral Smad1 and Smad2 proteins without exogenously added ligands induced inhibin B production, Levels of phosphorylated Smad2/3 are sensors of the interplay between effects of retinoic acid and TGF-beta or vitamin D3 on monocytic and granulocytic differentiation of HL-60 cells., Phenotypic and functional changes associated with TGF-beta1-induced fibroblast terminal differentiation are differentially regulated by Smad2, Smad3, and Smad4., TGF-beta1 inhibited IFN-gamma and TNF-alpha-induced TARC production in HaCaT cells via Smad2/3. Modulation of TGF-beta/Smad signaling pathway may be beneficial for treatment of atopic dermatitis., In SMAD4-negative cell lines, TGF-beta caused Smad2 to move to the nucleus in a Smad4-independent fashion. Nuclear translocation of Smad2 was not sufficient to activate reporters for TGF-beta-induced transcriptional responses., Results suggest that the Smad 2 may be the downstream signal transducers of TGF-beta(1) in human dental pulp cells., A deletion of 'G' in the L3 loop (crucial in Smad-receptor interaction) & an insertion of 'A' in codon 122 (loss of MH2 domain) in cervical tumor cells caused frame shift & pretermination in Smad2, highlighting its important role in these tumors., a signal transduction cascade of the TGF-beta/Smad signaling pathway, which is activated in the GEC, appears to be involved in the development of focal segmental glomerulosclerosis, Smad2, Smad3 and Smad4 contribute to the regulation of TGF-beta responses to varying extents, and exhibit distinct roles in different cell types, Tuberin (TSC2) interact with smad2/smad3 during TGF-beta1 growth regulation., The most transcriptionally active splice variants of Smad2 are made in macrophages (but not SMCs) of fibrofatty lesions and are upregulated after cell differentiation from monocytes. Cyclin inhibitors are induced by Smads. Fibrous plaque SMCs make Smad2., Differential gene expression of Smad2, a tumor suppressor gene, plays a significant role in the proliferation of breast cancer, Regulated cytoplasmic and nuclear retention may play a role in determining the distribution of Smads between the cytoplasm and the nucleus in both uninduced cells and upon TGF-beta induction., Smad2/3 is activated in undifferentiated human embryonic stem cells and required for the expression of genes controlling Nodal signaling, TGF-beta-stimulation of transcription of PAI-1 is inhibited by VEGF, and TGF-beta phosphorylation of Smad2/3, an obligatory step of intracellular TGF-beta signaling, is suppressed by VEGF, NEDD4-2 bound to TGF-beta-specific R-Smads, Smads 2 and 3, in a ligand-dependent manner, and induced degradation of Smad2, but not Smad3, p38 MAP kinase and Rho/ROCK pathways together with Smad2 and Smad3 are necessary for TGF-beta-mediated growth inhibition, caspase-3 is crucial for the differentiation of bone marrow stromal stem cells by influencing TGF-beta/Smad2 pathway and cell cycle progression, internalization is important for transforming growth factor beta1-induced Smad2 association with Smad anchor for receptor activation (SARA) and Smad2-dependent signaling in human mesangial cells, c-Jun NH(2)-terminal kinase tended to induce the phosphorylation of Smad2/3L in human colorectal adenoma-carcinoma sequence., TGF-beta signaling suppresses nuclear export of Smad4 by chromosome region maintenance 1 and targets Smad4 into the nucleus; mutations in Smad4 that affect its interaction with Smad2 or Smad3 impair nuclear accumulation of Smad4 in response to TGF-beta, UV-induced down-regulation of TbetaRII and the concerted over-expression of Smad7 may trigger the inhibition of the TGF-beta-induced phosphorylation of Smad2., Smad4, but not Smad2, mediates TGF-beta1-induced MMP-2 expression in invasive extravillous trophoblasts, Distinct roles for Smad2 and Smad3 in TGFbeta1-induced CTGF expression and markers of EMT in human PTECs are reported., TGF-beta-dependent nuclear accumulation of Smad2 is caused exclusively by selective nuclear trapping of phosphorylated, complexed Smad2, TGF-beta1 acts on adjacent stromal cells to turn on Smad2 signalling that could lead to stromal decidualization., Babo/dSmad2 signaling prior to metamorphosis may be widely required to prepare neurons for the dynamic environment present during metamorphosis., A novel missense mutation of SMAD2, located in exon 8 at codon 276 TCG (ser) -->TTG (leu), was identified in head and neck squamous cell carcinoma cell line SCC-15., Activation of Smad3 but not Smad2 is a key mechanism by which Angioteinsin ii mediates artriosclerosis., Our data indicate that TGF-beta1 induces endothelial barrier dysfunction involving Smad2-dependent p38 activation, resulting in RhoA activation by possible transcriptional regulation., These results suggest that p38 affects the phosphorylation of Smad2 and Smad3 differentially during TGF-beta signaling in human dental pulp cells and ERK1/2 might be involved in the process., identified the small C-terminal domain phosphatase 1 (SCP1) as a specific phosphatase for Smad2/3 dephosphorylation in the linker and N terminus, mRNA expressed in human granulosa-luteal cells at oocyte retrieval., Leptin and TGF-beta1 synergistically augmented activation of signalling components of mitogen-activated protein kinase (MAPK), STAT3 and Smad but did not modulate the expression of LEPR-B., Disruption of the TGF-beta 1-Smad2 signaling pathway may lead to the resistance of TGF-beta 1 growth-inhibitory effect on oral squamous cell carcinoma., High Smad2 is associated with glioma, Breast cancer wiwthw hight expression of cancerous phosphorylated Smad2 tended to have a better prognosis, although statistic significance was never reached., Platelets possess Smad2 protein and that its phosphorylation state is increased after exposure to TGF-beta1., High D-glucose increases L-arginine transport and eNOS expression following TbetaRII activation by TGF-beta1 involving p42/44(mapk) and Smad2 in HUVEC., Results define Erbin as a novel negative modulator of Smad2/Smad3 functions and expand the physiological role of Erbin to the regulation of TGFbeta signaling., The aberrant expressions of PTEN and phosphorylated Smad2 and their interaction may play an important role in the pathogenesis of hepatocellular carcinoma., Aberrant location of expression/staining intensity of PTEN, PPM1A and P-Smad2 in hepatocellular carcinoma may impact disease progression., Mutant p53 attenuates TGF-beta1 signaling. This was exhibited by a reduction in SMAD2/3 phosphorylation and an inhibition of both the formation of SMAD2/SMAD4 complexes and the translocation of SMAD4 to the cell nucleus., The expression of Smad2/3 in cervical cancer had no correlation to clinical stage, pathologic classification, histological grade, and lymph node involvement, but was positively correlated to HPV16 E7 infection., These findings suggest that CLU regulates TGF-beta signaling pathway by modulating the stability of Smad2/3 proteins., Activin A increased and follistatin decreased phosphorylation of SMAD2/3 in vitro, and activin increased SMAD2 and decreased KITLG mRNA expression., increased TGF-beta-Smad signaling in sporadic and familial ALS and impaired TGF-beta signal transduction in neurons of sporadic ALS patients, presumably at the step of pSmad2/3 translocation into the nucleus, TGF-beta mediates its effects on proteoglycan synthesis in VSMCs via the ALK5/Smad2/3 phosphorylation pathway as well as via the p38 MAP kinase signaling cascade., interaction between RAP250, Smad2, and Smad3 constitutes an important bridging mechanism linking LXR and TGF-beta signaling pathways., SMAD 2/3 signaling directly supports NANOG expression, while SMAD 1/5/8 activation moderately represses SOX2., PTEN abrogates TGF-beta-induced Smad2/3 phosphorylation. This study establishes a novel role for nuclear PTEN in the stabilization of PPM1A., PCTA defines a new component of the TGF-beta signalling pathway that functions to facilitate Smad2 phosphorylation through controlling the accumulation of cPML into the cytoplasm, and consequently, the assembly of Smad2-receptor complex., Data demonstrate that in response to TGFbeta stimulation the transcriptional regulator TAZ binds heteromeric Smad2/3-4 complexes and is recruited to TGFbeta response elements., Compared with normal skin fibroblasts, endogenous expression of Smad2 in hypertrophic skin fibroblasts was up-regulated and TGF-beta1 could further stimulate the production of Smad2., Keratinocyte-specific Smad2 ablation results in increased epithelial-mesenchymal transition during skin cancer formation and progression., the expression levels of TbetaRII and Smad2 in Sertoli Cell-Only Syndrome testes were upregulated compared to that in the normal controls., a number of putative novel Smad2 and Smad3 associated proteins in TGF-beta1 signaling were identified that have functions in cell proliferation, apoptosis, actin cytoskeleton regulation, cell motility, transcription, and Ras or insulin signaling, Activin stimulates endogenous inhibin alpha- and betaB-subunit mRNA, protein, and proteolytic processing. Simultaneously, activin stimulated the proconvertase furin through a Smad2/3-dependent process., SMAD2 is not shown to have a role in colorectal cancer with inflammatory bowel disease, Binding elements for ETS and transcription factor AP-2 (TFAP2) were significantly enriched in Smad2/3 binding sites, and knockdown of either ETS1 or TFAP2A resulted in overall alteration of TGF-beta-induced transcription., This study has demonstrated that constant cyclic stretching inhibits adipogenic differentiation of human umbilical cord progenitor cells via autocrine/paracrine stimulation of the TGFbeta1/Smad2 signaling pathway., Single nucleotide polymorphism in SMAD2 gene is associated with acute lymphoblastic leukemia., Data suggest that integrin alpha3beta1 is a critical coordinator of epithelial-mesenchyme transition signaling pathways involving beta-catenin and pSmad2., Pin1 negatively regulates TGF-beta signaling by down-regulating Smad2/3 protein levels via induction of Smurf2-mediated ubiquitin-proteasomal degradation., disruption of Smad2 function by CDK2 phosphorylation acts as a mechanism for TGF-beta resistance in multiple myeloma., RanBP3 directly recognizes dephosphorylated Smad2/3, which results from the activity of nuclear Smad phosphatases, and mediates nuclear export of Smad2/3 in a Ran-dependent manner., Ang II activation of Smad2 occurs via the AT1 receptor, but not the AT2 receptor, Results show that targeted disruption of the cell surface Cripto/GRP78 complex precludes Cripto activation of MAPK/PI3K and Smad2/3 pathways., The results suggest that 15d-PGJ(2) inhibits TGF-beta-induced CTGF expression by inhibiting the phosphorylation of Smad2., Study shows that Sp1 alone or the combination of Smad2 and Smad4 activated the alpha(1)(I) collagen promoter in transfected LX-2 stellate cells., SARA has a role in regulating cell phenotype and its effects are mediated through modification of the balance between Smad2 and Smad3 signaling, Study data demonstrates downregulated SMAD2 expression in psoriatic skin., Myostatin or 20 ng/mL BMP-11 maintain the colony and cellular morphology of undifferentiated hESC, maintain POU5f1, NANOG, TRA-1-60, and SSEA4 expression, and display increased SMAD2/3 phosphorylation, Data suggest that the SMAD family, possibly through disruption of SMAD1/5 or activation of SMAD2/3 may contribute to the pathogenesis of JGCT in humans., p130Cas is required for mammary tumor growth and transforming growth factor-beta-mediated metastasis through regulation of Smad2/3 activity, TGF-beta-mediated up-regulation of the expression of the integrin subunits alpha(2) and alpha(6) is mainly mediated in MSC by Smad2., Results identify Nedd4L as the ubiquitin ligase in TGF-beta induced phosphorylation of the transcription factors Smad2 and Smad3., Our data provide evidence that TGF-beta signaling patterns vary by age and pathologic features of prognostic significance including ER expression., Data show that upon hypoxia, the TGF-beta-induced phosphorylation of Smad3 was inhibited, although Smad2 remained phosphorylated, and Smad3 was dephosphorylated by PP2A., Smad2 knockdown resulted in a more aggressive breast cancer cells., Of 51 microsatellite stable colon tumors, 7 (14%) lost ACVR2, 2 (4%) ACVR1, and 5 (10%) pSMAD2 expression., Findings reveal a hyperactive TGFbeta-TGFbetaR-Smad2 signaling axis needed to maintain epigenetic silencing of critical EMT genes and breast cancer progression., feasible route for lactoferrin to transduce its antiproliferative effect in HeLa cells, We assessed the immunohistochemical expression profiles of Smad2, P-Smad2, Smad4, and p21/WAF1 proteins in 34 cases of osteosarcoma, BMP6, Smad1, Smad2 mRNA and protein expression were significantly higher in during sickle-cell pathology with orthopedic complications., Smad6 together with Smad2 may be prognostic factors, independent of nodal status in oral SCC after curative resection, Smad2 is rapidly phosphorylated by treatment with lipoic acid within 30 min, enhancing type I collagen synthesis through the activation of Smad signaling., The Smad2/3 pathway is the predominant TGFbeta1 signaling pathway inducing Il6 and inhibiting Il8 release in bronchial epithelial cells., TGFbeta1-induced Smad2 nuclear translocation is negatively regulated by intracellular Ca(2+) in OLI-neu cells and increased intracellular Ca(2+) concentrations block Smad2-mediated transcription of TGFbeta target genes., Smad2 loss causes HGF upregulation via loss of Smad2-mediated transcriptional repression and enhanced Smad3/4-mediated transactivation., Smad2/3 and p38 MAPK differentially regulate TGFB1-induced epithelial-mesenchymal transition in pulmonary epithelial cells., pattern of Smad2 activation supports a model in which TGFbeta/activin signaling is anti-atherogenic in the media of normal artery walls but is equally compatible with an anti-atherogenic or pro-atherogenic response to TGFbeta/activin in neointima of lesions., The Smad2 was highly expressed in VKC conjunctiva in association with TGF-b1., MicroRNA-155 has a role in targeting SMAD2 and modulating the response of macrophages to transforming growth factor-beta, SMAD2 polymorphisms may be one of genetic determinants of BMD in postmenopausal women, These findings indicate that IKKalpha contributes to the tumor-promoting function of the TGFbeta-SMAD signaling pathway in particular cancers., PARP-1 dissociates Smad complexes from DNA by ADP-ribosylating Smad3 and Smad4, which attenuates Smad-specific gene responses and TGF-beta-induced epithelial-mesenchymal transition., A strong negative correlation between LTBP-1 and P-Smad2 immunoreactivity was found, implying that LTBP-1 is not likely to contribute directly to the increased levels of TGF-beta activity in malignant mesothelioma., The expression of p-Smad2 is associated with malignant phenotype and poor prognosis in patients with advanced gastric carcinoma., results indicate that the DeltaNp63 promoter is activated by the keratinocyte-specific TGF-beta signaling mechanism with Smad2 and IKKalpha in squamous cell carcinomas, Data show that the WWP2-N isoform interacts with Smad2 and Smad3, whereas WWP2-C interacts only with Smad7., Activin A-ACVRIB/ALK4-Smad-dependent collagen production was augmented in SSc fibroblasts, suggesting the involvement of this signaling mechanism in systemic sclerosis., Findings offer insights into how MNK1 pathways control translation of cancer-related mRNAs including SMAD2, a key component of the TGF-beta signaling pathway., Smad2 was both preferentially phosphorylated in the linker region and localized to the nucleus in a flow-dependent manner, In malignant cells with a functional TGF-beta signalling pathway Rac1 antagonizes the TGF-beta1 growth inhibitory response and enhances cell migration by antagonistically regulating Smad2 and Smad3 activation, l type-specific target selection by combinatorial binding of Smad2/3 proteins and hepatocyte nuclear factor 4alpha in HepG2 cells., specific inhibition of SMAD-2/3 signaling pathway in hESCs facilitates the conversion of hESCs into multipotent MSCs with fully immunosuppresive and anti-inflammatory properties in vivo, opening up new avenues for potential future clinical applications., In middle cerebral artery occlusion-induced activation of Smad-binding elements (SBEs), a downstream target of Smad 2/3 transcription factors regulates expression of the luciferase reporter., HEB and E2A-bind the SCA motif at regions overlapping SMAD2/3 and FOXH1, we describe TGF-beta signalling through Smad2/3 and the importance of the linker region in the regulation and expression of genes induced by TGF-beta--{REVIEW}, Protein phosphatase PPM1A regulates the nuclear export of Smad2/3 through targeting nuclear exporter RanBP3., Both androgen-sensitive and castration-resistant prostate cancer cell lines demonstrate TGF-beta1-induced phosphorylation and nuclear translocation of Smad2/3 that is robust in metastatic lines., Data suggest that TGF-beta, TGF-betaR1, TGF-betaR2, Smad4, pSmad2/3, and E-cadherin are closely related to tumor-node-metastasis (TNM) stage of colorectal cancer (CRC)., Smad2 copy-number variations are associated with basal cell carcinoma, squamous cell carcinoma in skin cancers., When PI3K/Akt signaling is low, Wnt effectors are activated and function in conjunction with Smad2,3 to promote differentiation, miR-155 may function as a tumor suppressor to regulate gastric cancer cell metastasis by targeting SMAD2, and its downregulation in gastric cancer cells may be partly ascribed to DNA methylation., Data suggest that the formation of transient TIF1gamma-Smad2-Smad4 ternary complexes is the only one that can account for TGF-beta signaling., Data show that dSmad2 directly influences Baboon's phosphorylation of Mad., TGF-beta family signaling through Smads is conceptually a simple and linear signaling pathway, driven by sequential phosphorylation, with type II receptors activating type I receptors, which in turn activate R-Smads [review], The TGF-beta-mediated regulation of CD36, lipoprotein lipase and scavenger receptor-A gene expression was dependent on Smad-2., analysis of the dynamics of TGF-beta and Smad2/Smad3 signaling [review], Immunohistochemical analysis of phosphorylated Smad2 showed nuclear expression in 70% of the osteosarcoma samples at levels comparable to osteoblastoma. Cases with lower expression showed significantly worse disease free survival., Suggest that TGFbeta1/Smad2 signalling pathway of T cells is altered in patients with Behcet's disease., Diseased aortic valve leaflets demonstrated strong immunohistochemical staining for transforming growth factor-beta1 and phosphorylated Smad2/3., The non-canonical increase in Smad linker phosphorylation induced by riluzole could contribute to the modulation of the pro-oncogenic functions of Smad2 and Smad3 in late stage melanomas., The prevalence of SMAD4, SMAD2, and SMAD3 mutations in sporadic CRCs was 8.6% (64 of 744), 3.4% (25 of 744), and 4.3% (32 of 744), respectively., Binding of Activin-A-responsive SMAD2 to the NKX2-1 promoter plays essential role during respiratory endoderm specification., increased activation in thoracic aortic aneurysms, SDC-2 modulates TGFbeta2 transcriptional regulation via Smad2 signaling to facilitate fibrosarcoma cell adhesion., SMAD2 and SMAD3 acetylatation by P300-CBP is mediated by TGFB1 in human lung cancer cells., show that Araf antagonizes mesendoderm induction and patterning activity of Nodal/Smad2 signals in vertebrate embryos by directly inhibiting Smad2 signalling, Findings indicate that Smad2 is a unique integrator of transcription and signaling events and is essential for the maintenance of the mouse and human primed pluripotent stem cell state., Context-dependent responses to Smad2/3 imposed by Polycomb action provide a mechanism for selective gene regulation that can reconcile the apparently conflicting roles of this signaling pathway in pluripotency, differentiation, and reprogramming., The signaling activation triggered by overexpression of Smad2 was dependent on TGF-beta type I receptor, increased p15 and p21 expression, responsible for inhibiting cell cycle entry, resulting in antiproliferative effects on gingival epithelial cells., Smad2 is required for transcription of the aromatase gene in the KGN cells., a nuclear envelope-localized mechanism of inactivating TGF-beta signaling in which MAN1 competes with transcription factors for binding to Smad2 and Smad3 and facilitates their dephosphorylation by PPM1A., a detailed computational model for TGF-beta signalling that incorporates elements of previous models together with crosstalking between Smad1/5/8 and Smad2/3 channels through a negative feedback loop dependent on Smad7., Smad2 regulated protease nexin-1 up-regulation differentiates chronic aneurysm development from acute aortic dissection., Data show that miR-148a downregulated vimentin expression and upregulated E-cadherin expression, suggesting that miR-148a inhibited epithelial-mesenchymal transition (EMT), and the SMAD2 gene was identified as the direct and functional target of miR-148a., miR-18b regulated the TGF-beta1-induced differentiation of miR-18b regulated the TGF-beta1-induced differentiation of hair follicle mesenchymal stem cells into smooth muscle cells by targeting SMAD2 gene., One SNP in the SMAD2 gene having association with chronic otitis media with effusion in study population., Smad2 and PIAS1 proteins were significantly upregulated resulting in dramatically increased interactions between Smad2/4 and PIAS1 in the presence of zinc., TRPV1 potentiates TGFbeta-induction of corneal myofibroblast development through an oxidative stress-mediated p38-SMAD2 signaling loop., inhibition of Smad2/3 by siRNA significantly decreased the production of IL-6 and VEGF in mesenchymal stem cells and induced their osteogenic differentiation, Smad2 promotes the tumor progression by upregulating the CDK2, CDK4, and cyclin E., Glucocorticoids recruit Tgfbr3 and Smad1 to shift transforming growth factor-beta signaling from the Tgfbr1/Smad2/3 axis to the Acvrl1/Smad1 axis in lung fibroblasts., Nodal expression was significantly upregulated in glioma cells when TGF-beta was added, whereas the TGF-beta-induced Nodal expression was evidently inhibited by transfection Smad2 or Smad3 siRNAs., Phosphorylated Smad2 is enriched in recurrent compared with matched-primary ovarian tumors., High expression of IGFBP7 in fibroblasts induced by colorectal cancer cells is co-regulated by TGF-beta and Wnt signaling in a Smad2/3-Dvl2/3-dependent manner., Using a human CTL system model based on a CD8(+)/CD103(-) T cell clone specific of a lung tumor-associated Ag, we demonstrated that the transcription factors Smad2/3 and NFAT-1 are two critical regulators of this process., Galectin-1 stimulates motility of human umbilical cord blood-derived mesenchymal stem cells by downregulation of smad2/3-dependent COL3A1/COL5A1 and upregulation of NF-kappaB-dependent fibronectin/laminin 5 expression., Respiratory exposure to multi-walled carbon nanotubes induced length dependent pulmonary fibrosis and epithelial-derived fibroblasts via TGF-beta1/Smad2 pathway., data suggest that PGE2 had no effects on Smad2 phosphorylation, suggesting that PGE2-mediated Smad2-Smad4 complex formation is independent of TGF-beta signaling, Data indicate that miR-18a could regulate trophoblast Cell invasion via targeting Smad2., Nodal promotes the self-renewal of human colon cancer stem cells and mediate carcinogenesis of human colorectal cancer via an autocrine manner through Smad2/3 pathway., Mutations in SMAD2 may be a cause of as much as 10% of all congenital heart disease., These results suggest that ZNF580 mediates eNOS expression and endothelial cell migration/proliferation via the TGF-b1/ALK5/Smad2 pathway, and thus plays a crucial role in vascular endothelial cells., Data suggest that extracellular signal-regulated kinases ERK1/2 signaling can cross-interact with the transforming growth factor beta2/Smad2/3 and the Jagged-1/Notch-3 signaling in retinal pigment epithelium cells epithelial-mesenchymal transition., The current findings indicate miR-146a plays an important role in skeletogenesis through attenuation of SMAD2 and SMAD3 function., Smad2 and Smad3 are both necessary for the formation of posterior capsular opacification of human lens epithelial cells., In conclusion, this study identifies opposing roles for Smad2 and Smad3 in peritoneal dialysis-associated peritoneal fibrosis, Activin A, B, and AB produce comparable increases in human trophoblast cell invasion by up-regulating N-cadherin expression in a SMAD2/3-SMAD4-dependent manner., Study has revealed miR-27a as a tumor suppressor and has identified SGPP1 and Smad2 as novel targets of miR-27a, linking to STAT3 for regulating cancer cell proliferation, apoptosis and migration in colorectal cancer., miR-136 may play a tumor-suppressive role by repressing EMT and prometastatic traits via targeting Smad2 and Smad3., The expression levels of collagens type I/III, TGF-beta1, Smad2/3/4/7 and PAI-1 (plasminogen activator inhibitor type 1) in gluteal muscle contraction (GMC) patients were measured., A role for decorin and p-Smad-2 in the pathophysiology of fetal membranes and adverse pregnancy outcomes., Lefty reduced the levels of phosphorylated Smad2, Smad3, and ERK1/2, inhibited the proliferation and invasion of glioma cells, and increased their apoptosis., We found that induction of SMAD2 in HCC cells completely abolished the inhibitory effect of NH4Cl on rapamycin-induced autophagy in HCC cells, suggesting that NH4Cl inhibits autophagy of HCC cells through inhibiting SMAD2 signaling., knockdown of Smad3 significantly reduced TGF-beta1-induced Col.I production. These findings were further evident by the results that overexpression of Smad2 attenuated the expression of Col.I and TIMP-1, High p-Smad2 expression in stromal fibroblasts is associated with non-small cell lung cancer., Ca2+- and KCa3.1-dependent processes facilitate "constitutive" alpha smooth muscle actin expression and Smad2/3 signalling in IPF-derived fibroblasts, and thus promote fibroblast to myofibroblast differentiation., Together, our findings defined an essential role for the KMT1E/SMAD2/3 repressor complex in TGFbeta-mediated lung cancer metastasis., A cytoplasmic predominant TGF-betaRII expression pattern and a higher pSmad2 expression were associated with decreased breast cancer survival., Nodal induces signal transduction through the Smad2/3-dependent pathway in vitro. Results that Nodal promotes pancreatic cancer cell migration and invasion and induces epithelial-mesenchymal transition., MicroRNA-10a silencing reverses cisplatin resistance in the A549/cisplatin human lung cancer cell line via the transforming growth factor-beta/Smad2/STAT3/STAT5 pathway, TGF-beta/Smad2/Smad3 signal pathway is involved in glioma tumor cells proliferation and apoptosis., DEANR1 facilitates FOXA2 activation by facilitating SMAD2/3 recruitment to the FOXA2 promoter, smad2 and Erk/Akt have roles in TGF-beta1-induced apoptosis in human gingival epithelial cells, the findings of the present study suggest that H2O2 contributes to HUVEC apoptosis by inducing Nox4-dependent ROS aggregation and activating the TGF-beta1/Smad2 signaling pathway., Induction of neural crest genes by beta-catenin is repressed by SMAD2/SMAD3, ensuring proper lineage specification., These findings uncover a plausible mechanism for NF-kappaB-sustained TGF-beta/Smad activation via miR-148a in glioblastoma., Report inhibition of colorectal cancer stem cell survival and invasive potential by hsa-miR-140-5p mediated suppression of Smad2 and autophagy., study indicated that miR-212/132 functions as tumor suppressor by targeting SMAD2 in cervical cancer, Neovibsanin B utilizes the canonical Smad signalling pathway to stimulate ECM synthesis in human optic nerve head cells., Studies demonstrated that MUC1-mediated JNK activation not only enhances the phosphorylation of Smad2 C-terminal at Ser-465/467 site (Smad2C) through TGF-beta/TbetaRI, but also enhances the phosphorylation of Smad2 linker region at Ser-245/250/255 site., we show, for the first time, that SMAD2 signaling is directly regulated by HDAC6, SMAD2 mutations are associated with arterial aneurysms and dissections, Astragaloside can delay the renal fibrosis process in diabetic mice by influencing the TGF-beta/SMADS signaling pathway and down-regulating TGF-beta1, SMAD2/3, and alpha-SMA expression., Suggest that TGF-beta1/Smad and Wnt/CTNNB1 signaling pathways both contribute to pathological scar formation., Different signaling pathways are involved in osteitis in CRS and are activated by the TGF-beta/Smad signaling pathway in CRSwNP versus the TGF-beta/Smad-independent signaling pathway in CRSsNP., Follistatin-like 1 attenuates differentiation and survival of erythroid cells through Smad2/3 signaling., Relationship between Expression of TGF-beta1, Smad2, Smad4 and Prognosis of Patients with Resected Non-small Cell Lung Cancer, Up-regulation of smad2 is associated with endometrial cancer., TGF-beta/Smad signalling pathway and VEGF-A participate in the pathogenesis of sarcoidosis., The present study thus proposed SEB as an agent able to significantly reduce Smad2/3 expression in colon cancer cells, provoking moderate TGFb growth signaling and the reduction of tumor cell proliferation., Data suggest SHC1 (SH2 domain protein C1) expression down-regulates epithelial-mesenchymal transition by repressing TGFB-induced SMAD2/3 activation through differential partitioning of receptors at cell surface of mammocytes/keratinocytes., correlation between TGFb1 and pSmad2 as well as between HtrA1 and TGFb1 and the very significant increase of Ki67 in stromal compartment of eutopic endometrium suggest a possible involvement of HtrA1 in the pathogenesis of endometriosis., data suggest that TGF-beta1 enhances IGFBP7 via Smad2/4 pathways, and that IGFBP7 might be involved in the TGF-beta1-induced tubular injury in DN.,
SP_COMMENT disease:Defects in SMAD2 are found in sporadic cases of colorectal carcinoma., function:Transcriptional modulator activated by TGF-beta and activin type 1 receptor kinase. SMAD2 is a receptor-regulated SMAD (R-SMAD). May act as a tumor suppressor in colorectal carcinoma., PTM:Acetylated on Lys-19 by coactivators in response to TGF-beta signaling, which increases transcriptional activity. Isoform short: Acetylation increases DNA binding activity in vitro and enhances its association with target promoters in vivo., PTM:In response to TGF-beta, ubiquitinated by NEDD4L; which promotes its degradation., PTM:Phosphorylated on one or several of Thr-220, Ser-245, Ser-250, and Ser-255. In response to TGF-beta, phosphorylated on Ser-465/467 by TGF-beta and activin type 1 receptor kinases. Able to interact with SMURF2 when phosphorylated on Ser-465/467, recruiting other proteins, such as SNON, for degradation. In response to decorin, the naturally occurring inhibitor of TGF-beta signaling, phosphorylated on Ser-240 by CaMK2. Phosphorylated by MAPK3 upon EGF stimulation; which increases transcriptional activity and stability, and is blocked by calmodulin., similarity:Belongs to the dwarfin/SMAD family., similarity:Contains 1 MH1 (MAD homology 1) domain., similarity:Contains 1 MH2 (MAD homology 2) domain., subcellular location:Cytoplasmic in the absence of ligand. Migrates to the nucleus when complexed with SMAD4., subunit:Found in a complex with SMAD3 and TRIM33 upon addition of TGF-beta. Interacts with SMAD3 and TRIM33. Interacts with SARA (SMAD anchor for receptor activation); may form trimers with the SMAD4 co-SMAD. Interacts with FOXH1, homeobox protein TGIF, PEBP2-alpha subunit, CREB-binding protein (CBP), EP300 and SKI. Interacts with SNON; when phosphorylated at Ser-465/467. Interacts (via PY-motif) with SMURF2. Interacts with AIP1 and HGS. Interacts with NEDD4L in response to TGF-beta (By similarity). Interacts with LBXCOR1 and CORL2., tissue specificity:Expressed at high levels in skeletal muscle, heart and placenta.,