Genomes and Genes
Summary: A receptor-regulated smad protein that undergoes PHOSPHORYLATION by BONE MORPHOGENETIC PROTEIN RECEPTORS. It regulates BONE MORPHOGENETIC PROTEIN signaling and plays an essential role in EMBRYONIC DEVELOPMENT.
- Takahashi T, Abe H, Arai H, Matsubara T, Nagai K, Matsuura M, et al. Activation of STAT3/Smad1 is a key signaling pathway for progression to glomerulosclerosis in experimental glomerulonephritis. J Biol Chem. 2005;280:7100-6 pubmed..These data suggest that the activation of STAT3 and Smad1 participates in the developing process of glomerulosclerosis in experimental glomerulonephritis. ..
- Fukuda S, Abematsu M, Mori H, Yanagisawa M, Kagawa T, Nakashima K, et al. Potentiation of astrogliogenesis by STAT3-mediated activation of bone morphogenetic protein-Smad signaling in neural stem cells. Mol Cell Biol. 2007;27:4931-7 pubmed..Our study suggests a novel LIF-triggered positive regulatory loop that enhances astrogliogenesis. ..
- Nudi M, Ouimette J, Drouin J. Bone morphogenic protein (Smad)-mediated repression of proopiomelanocortin transcription by interference with Pitx/Tpit activity. Mol Endocrinol. 2005;19:1329-42 pubmed..It is postulated that these interactions interfere with the transcriptional activity of Pitx and/or Tpit, thus resulting in transcriptional repression. ..
- Messenger N, Kabitschke C, Andrews R, Grimmer D, Nunez Miguel R, Blundell T, et al. Functional specificity of the Xenopus T-domain protein Brachyury is conferred by its ability to interact with Smad1. Dev Cell. 2005;8:599-610 pubmed..These findings suggest a mechanism by which individual T-domain proteins may interact with different partners to elicit a specific response. ..
- Morikawa M, Koinuma D, Tsutsumi S, Vasilaki E, Kanki Y, Heldin C, et al. ChIP-seq reveals cell type-specific binding patterns of BMP-specific Smads and a novel binding motif. Nucleic Acids Res. 2011;39:8712-27 pubmed publisher..These results provide insights into the molecular mechanism of BMP signaling and the pathogenesis of vascular lesions of certain genetic disorders, including hereditary hemorrhagic telangiectasia...
- Retting K, Song B, Yoon B, Lyons K. BMP canonical Smad signaling through Smad1 and Smad5 is required for endochondral bone formation. Development. 2009;136:1093-104 pubmed publisher..Finally, we tested whether FGF exerts its antagonistic effects directly through Smad linker phosphorylation. The results support the alternative conclusion that the effects of FGFs on BMP signaling are indirect in vivo. ..
- Abe H, Tominaga T, Matsubara T, Abe N, Kishi S, Nagai K, et al. Scleraxis modulates bone morphogenetic protein 4 (BMP4)-Smad1 protein-smooth muscle ?-actin (SMA) signal transduction in diabetic nephropathy. J Biol Chem. 2012;287:20430-42 pubmed publisher..These data suggest that Scx and Id1 are involved in the BMP4-Smad1-SMA signal transduction pathway besides the TGF?1-Smad1-SMA signaling pathway and modulate phenotypic changes in MCs in diabetic nephropathy...
- Darby S, Cross S, Brown N, Hamdy F, Robson C. BMP-6 over-expression in prostate cancer is associated with increased Id-1 protein and a more invasive phenotype. J Pathol. 2008;214:394-404 pubmed..001) across all samples for both benign and cancer cases. These data demonstrate that BMP-6 promotes migration and invasion of prostate cancer cells, potentially through activation of Id-1 and MMP activation. ..
- Craft C, Romero D, Vary C, Bergan R. Endoglin inhibits prostate cancer motility via activation of the ALK2-Smad1 pathway. Oncogene. 2007;26:7240-50 pubmed..These findings provide the first evidence that endoglin decreases PCa cell motility through activation of the ALK2-Smad1 pathway. ..
- Sapkota G, Alarcon C, Spagnoli F, Brivanlou A, Massague J. Balancing BMP signaling through integrated inputs into the Smad1 linker. Mol Cell. 2007;25:441-54 pubmed..The interplay between linker phosphorylation, Smurf-dependent ubiquitination, and nucleoporin exclusion enables regulation of BMP action by diverse signals and biological contexts. ..
- Wang Q, Wei X, Zhu T, Zhang M, Shen R, Xing L, et al. Bone morphogenetic protein 2 activates Smad6 gene transcription through bone-specific transcription factor Runx2. J Biol Chem. 2007;282:10742-8 pubmed..Treatment with BMP-2 and transfection of Smad1 abolished Smurf1 binding to the OSE2 site. These results show that Smad1 binding excludes Smurf1 interaction with the OSE2 site and promotes Smad6 gene transcription. ..
- Brown C, Chi X, Garcia Gras E, Shirai M, Feng X, Schwartz R. The cardiac determination factor, Nkx2-5, is activated by mutual cofactors GATA-4 and Smad1/4 via a novel upstream enhancer. J Biol Chem. 2004;279:10659-69 pubmed
- Matsubara T, Abe H, Arai H, Nagai K, Mima A, Kanamori H, et al. Expression of Smad1 is directly associated with mesangial matrix expansion in rat diabetic nephropathy. Lab Invest. 2006;86:357-68 pubmed..Our data imply that urinary Smad1 might be a representative diagnostic marker for mesangial matrix expansion in diabetic nephropathy. ..
- Monteiro R, de Sousa Lopes S, Korchynskyi O, Ten Dijke P, Mummery C. Spatio-temporal activation of Smad1 and Smad5 in vivo: monitoring transcriptional activity of Smad proteins. J Cell Sci. 2004;117:4653-63 pubmed..We have thus generated, for the first time, an in vivo readout for studying the role of Smad1/5-mediated transcriptional activity in development. ..
- Munoz O, Fend F, de Beaumont R, Husson H, Astier A, Freedman A. TGFbeta-mediated activation of Smad1 in B-cell non-Hodgkin's lymphoma and effect on cell proliferation. Leukemia. 2004;18:2015-25 pubmed..This work opens new insights into aberrant Smad pathways and their pathophysiological role in FL and in other non-Hodgkin lymphomas. ..
- Pannu J, Asano Y, Nakerakanti S, Smith E, Jablonska S, Blaszczyk M, et al. Smad1 pathway is activated in systemic sclerosis fibroblasts and is targeted by imatinib mesylate. Arthritis Rheum. 2008;58:2528-37 pubmed publisher..This study suggests that SSc patients with activated Smad1 signaling may benefit from imatinib mesylate treatment. ..
- Goumans M, Valdimarsdottir G, Itoh S, Lebrin F, Larsson J, Mummery C, et al. Activin receptor-like kinase (ALK)1 is an antagonistic mediator of lateral TGFbeta/ALK5 signaling. Mol Cell. 2003;12:817-28 pubmed..TGFbeta type II receptor is also required for ALK1 activation by TGFbeta. Interestingly, ALK1 not only induces a biological response opposite to that of ALK5 but also directly antagonizes ALK5/Smad signaling. ..
- Parikh P, Hao Y, Hosseinkhani M, Patil S, Huntley G, Tessier Lavigne M, et al. Regeneration of axons in injured spinal cord by activation of bone morphogenetic protein/Smad1 signaling pathway in adult neurons. Proc Natl Acad Sci U S A. 2011;108:E99-107 pubmed publisher..Together, our results identify a therapeutic target to promote axonal regeneration after SCI. ..
- Fukuda T, Kohda M, Kanomata K, Nojima J, Nakamura A, Kamizono J, et al. Constitutively activated ALK2 and increased SMAD1/5 cooperatively induce bone morphogenetic protein signaling in fibrodysplasia ossificans progressiva. J Biol Chem. 2009;284:7149-56 pubmed publisher..Gene transfer of Smad7 or inhibition of type I receptors with dorsomorphin may represent strategies for blocking the activity induced by ALK2(R206H) in FOP...
- Orvis G, Jamin S, Kwan K, Mishina Y, Kaartinen V, Huang S, et al. Functional redundancy of TGF-beta family type I receptors and receptor-Smads in mediating anti-Mullerian hormone-induced Mullerian duct regression in the mouse. Biol Reprod. 2008;78:994-1001 pubmed publisher..Loss of these genes in the Müllerian duct mesenchyme results in male infertility due to retention of Müllerian duct derivatives in an otherwise virilized male. ..
- Pangas S, Li X, Umans L, Zwijsen A, Huylebroeck D, Gutierrez C, et al. Conditional deletion of Smad1 and Smad5 in somatic cells of male and female gonads leads to metastatic tumor development in mice. Mol Cell Biol. 2008;28:248-57 pubmed..These data strongly implicate the BR-SMADs as part of a critical developmental pathway in ovaries and testis that, when disrupted, leads to malignant transformation...
- Mitsui N, Suzuki N, Maeno M, Yanagisawa M, Koyama Y, Otsuka K, et al. Optimal compressive force induces bone formation via increasing bone morphogenetic proteins production and decreasing their antagonists production by Saos-2 cells. Life Sci. 2006;78:2697-706 pubmed..This study demonstrates that an optimal compressive force stimulates in vitro mineralization via increasing BMPs production and decreasing their antagonists production. ..
- Liu Z, Tang Y, Qiu T, Cao X, Clemens T. A dishevelled-1/Smad1 interaction couples WNT and bone morphogenetic protein signaling pathways in uncommitted bone marrow stromal cells. J Biol Chem. 2006;281:17156-63 pubmed..Expression of a mutant Smad1 protein, which cannot be phosphorylated in response to BMP, eliminated the inhibitory effect of BMP on Wnt-inducedbeta-..
- Arnold S, Maretto S, Islam A, Bikoff E, Robertson E. Dose-dependent Smad1, Smad5 and Smad8 signaling in the early mouse embryo. Dev Biol. 2006;296:104-18 pubmed..These experiments demonstrate for the first time that Smad1 and Smad5 function cooperatively to govern BMP target gene expression in the early mammalian embryo. ..
- Morris E, Chrobak I, Bujor A, Hant F, Mummery C, Ten Dijke P, et al. Endoglin promotes TGF-?/Smad1 signaling in scleroderma fibroblasts. J Cell Physiol. 2011;226:3340-8 pubmed publisher..In conclusion, this study has revealed an important profibrotic role of endoglin in SSc fibroblasts. The endoglin/ALK1/Smad1 pathway could be a therapeutic target in patients with SSc if appropriately blocked. ..
- Herrera B, Van Dinther M, Ten Dijke P, Inman G. Autocrine bone morphogenetic protein-9 signals through activin receptor-like kinase-2/Smad1/Smad4 to promote ovarian cancer cell proliferation. Cancer Res. 2009;69:9254-62 pubmed publisher..Our data indicate that BMP9 signaling through ALK2 may be a novel therapeutic target in ovarian cancer. ..
- Aubin J, Davy A, Soriano P. In vivo convergence of BMP and MAPK signaling pathways: impact of differential Smad1 phosphorylation on development and homeostasis. Genes Dev. 2004;18:1482-94 pubmed..These results underscore the need to tightly balance BMP and MAPK signaling pathways through Smad1. ..
- Sammar M, Stricker S, Schwabe G, Sieber C, Hartung A, Hanke M, et al. Modulation of GDF5/BRI-b signalling through interaction with the tyrosine kinase receptor Ror2. Genes Cells. 2004;9:1227-38 pubmed..These results indicate for the first time a direct interaction of Ser/Thr- and Tyr-Kinase receptors and provide evidence for modulation of the Smad-pathway and GDF5 triggered chondrogenesis. ..
- Fei T, Xia K, Li Z, Zhou B, Zhu S, Chen H, et al. Genome-wide mapping of SMAD target genes reveals the role of BMP signaling in embryonic stem cell fate determination. Genome Res. 2010;20:36-44 pubmed publisher..Combined with computational analysis, our results suggest that SMAD-mediated BMP signaling balances self-renewal versus differentiation by modulating a set of developmental regulators. ..
- Alarcon C, Zaromytidou A, Xi Q, Gao S, Yu J, Fujisawa S, et al. Nuclear CDKs drive Smad transcriptional activation and turnover in BMP and TGF-beta pathways. Cell. 2009;139:757-69 pubmed publisher..Thus, nuclear CDK8/9 drive a cycle of Smad utilization and disposal that is an integral part of canonical BMP and TGF-beta pathways. ..
- Hardwick J, van den Brink G, Bleuming S, Ballester I, Van Den Brande J, Keller J, et al. Bone morphogenetic protein 2 is expressed by, and acts upon, mature epithelial cells in the colon. Gastroenterology. 2004;126:111-21 pubmed..BMP2 expression is lost in the microadenomas of familial adenomatous polyposis patients. These data suggest that BMP2 acts as a tumor suppressor promoting apoptosis in mature colonic epithelial cells. ..
- Cho Y, Kim W, Yoon W, Woo K, Baek J, Lee G, et al. Wnt3a stimulates Mepe, matrix extracellular phosphoglycoprotein, expression directly by the activation of the canonical Wnt signaling pathway and indirectly through the stimulation of autocrine Bmp-2 expression. J Cell Physiol. 2012;227:2287-96 pubmed publisher..Collectively, Wnt3a stimulates Mepe transcription directly by a canonical Wnt signaling pathway through ?-catenin and Lef-1 and indirectly through the activation of a Bmp-2 autocrine loop. ..
- Nakerakanti S, Bujor A, Trojanowska M. CCN2 is required for the TGF-? induced activation of Smad1-Erk1/2 signaling network. PLoS ONE. 2011;6:e21911 pubmed publisher..In conclusion, our study defines a novel CCN2/?(v)?(3) integrin/Src/Smad1 axis that contributes to the pro-fibrotic TGF-? signaling and suggests that blockade of this pathway may be beneficial for the treatment of fibrosis. ..
- Pera E, Ikeda A, Eivers E, De Robertis E. Integration of IGF, FGF, and anti-BMP signals via Smad1 phosphorylation in neural induction. Genes Dev. 2003;17:3023-8 pubmed..This hard-wired molecular mechanism at the level of the Smad1 transcription factor may help explain the opposing activities of IGF, FGF, and BMP signals not only in neural induction, but also in other aspects of vertebrate development. ..
- Takizawa T, Ochiai W, Nakashima K, Taga T. Enhanced gene activation by Notch and BMP signaling cross-talk. Nucleic Acids Res. 2003;31:5723-31 pubmed..These data suggest a novel functional cooperation between Notch signaling and BMP signaling. ..
- Chen C, Chen H, Sun J, Bringas P, Chen Y, Warburton D, et al. Smad1 expression and function during mouse embryonic lung branching morphogenesis. Am J Physiol Lung Cell Mol Physiol. 2005;288:L1033-9 pubmed..The dynamic expression patterns of Smad1 in embryonic mouse lungs were examined using immunohistochemistry. Smad1 protein was predominantly detected in peripheral airway epithelial cells of early embryonic lung tissue [embryonic day ..
- Kim D, Lassar A. Smad-dependent recruitment of a histone deacetylase/Sin3A complex modulates the bone morphogenetic protein-dependent transcriptional repressor activity of Nkx3.2. Mol Cell Biol. 2003;23:8704-17 pubmed
- Fuentealba L, Eivers E, Ikeda A, Hurtado C, Kuroda H, Pera E, et al. Integrating patterning signals: Wnt/GSK3 regulates the duration of the BMP/Smad1 signal. Cell. 2007;131:980-93 pubmed..Epistatic experiments suggested that the dorsoventral (BMP) and anteroposterior (Wnt/GSK3) patterning gradients are integrated at the level of Smad1 phosphorylations during embryonic pattern formation. ..
- Hu M, Wasserman D, Hartwig S, Rosenblum N. p38MAPK acts in the BMP7-dependent stimulatory pathway during epithelial cell morphogenesis and is regulated by Smad1. J Biol Chem. 2004;279:12051-9 pubmed..We conclude that BMP7 stimulates renal epithelial cell morphogenesis via p38(MAPK) and that p38(MAPK) activity is negatively regulated by Smad1. ..
- Abe H, Matsubara T, Iehara N, Nagai K, Takahashi T, Arai H, et al. Type IV collagen is transcriptionally regulated by Smad1 under advanced glycation end product (AGE) stimulation. J Biol Chem. 2004;279:14201-6 pubmed
- Qiu T, Grizzle W, Oelschlager D, Shen X, Cao X. Control of prostate cell growth: BMP antagonizes androgen mitogenic activity with incorporation of MAPK signals in Smad1. EMBO J. 2007;26:346-57 pubmed
- Wagner T, Kraeussling M, Fedorov L, Reiss C, Kneitz B, Schartl M. STAT3 and SMAD1 signaling in Medaka embryonic stem-like cells and blastula embryos. Stem Cells Dev. 2009;18:151-60 pubmed publisher..These results suggest that the signaling pathways active in the mouse ES-cell culture system represent the exception, while inactivity of STAT3 is apparently the rule in vertebrate ES-cell cultures. ..
- Baburajendran N, Palasingam P, Narasimhan K, Sun W, Prabhakar S, Jauch R, et al. Structure of Smad1 MH1/DNA complex reveals distinctive rearrangements of BMP and TGF-beta effectors. Nucleic Acids Res. 2010;38:3477-88 pubmed publisher..These findings suggest that Smad1 and Smad3 evolved differential qualities to assemble on composite DNA elements and to engage in co-factor interactions by remodeling their N-termini. ..
- Finnson K, Parker W, Ten Dijke P, Thorikay M, Philip A. ALK1 opposes ALK5/Smad3 signaling and expression of extracellular matrix components in human chondrocytes. J Bone Miner Res. 2008;23:896-906 pubmed publisher..Our results suggest that ALK1 and ALK5 display opposing functions in human chondrocytes, implicating an essential role for ALK1 in the regulation of TGF-beta signaling and function in these cells. ..
- Mima A, Matsubara T, Arai H, Abe H, Nagai K, Kanamori H, et al. Angiotensin II-dependent Src and Smad1 signaling pathway is crucial for the development of diabetic nephropathy. Lab Invest. 2006;86:927-39 pubmed..Taken together, these results indicate that Ang II can regulate the development of mesangial matrix expansion in the early phase of diabetic nephropathy through Src and Smad1. ..
- Lakshman M, Huang X, Ananthanarayanan V, Jovanovic B, Liu Y, Craft C, et al. Endoglin suppresses human prostate cancer metastasis. Clin Exp Metastasis. 2011;28:39-53 pubmed publisher..Endoglin is shown for the first time to suppress cell movement out of primary tumor as well as the formation of distant metastasis. It is also shown to co-regulate tumor growth and metastatic behavior in human PCa. ..
- Mima A, Arai H, Matsubara T, Abe H, Nagai K, Tamura Y, et al. Urinary Smad1 is a novel marker to predict later onset of mesangial matrix expansion in diabetic nephropathy. Diabetes. 2008;57:1712-22 pubmed publisher..These data indicate that urinary Smad1 could be a novel predictor for later onset of morphological changes and can be used to monitor the effect of ARBs in diabetic nephropathy. ..
- Tian H, Mythreye K, Golzio C, Katsanis N, Blobe G. Endoglin mediates fibronectin/?5?1 integrin and TGF-? pathway crosstalk in endothelial cells. EMBO J. 2012;31:3885-900 pubmed publisher..These studies provide a novel mechanism for the regulation of TGF-? superfamily signalling and endothelial function through crosstalk with integrin signalling pathways. ..
- Upton P, Long L, Trembath R, Morrell N. Functional characterization of bone morphogenetic protein binding sites and Smad1/5 activation in human vascular cells. Mol Pharmacol. 2008;73:539-52 pubmed..These cell-specific differences in BMP responses are important for understanding the pathogenesis of FPAH. ..
- Gao S, Laughon A. Flexible interaction of Drosophila Smad complexes with bipartite binding sites. Biochim Biophys Acta. 2007;1769:484-96 pubmed..Finally, we show that Smad1 and Smad4 can participate in binding to bipartite sites. ..
- Yang X, Long L, Southwood M, Rudarakanchana N, Upton P, Jeffery T, et al. Dysfunctional Smad signaling contributes to abnormal smooth muscle cell proliferation in familial pulmonary arterial hypertension. Circ Res. 2005;96:1053-63 pubmed..We conclude that defective Smad signaling and unopposed p38(MAPK)/ERK signaling, as a consequence of mutation in BMPR2, underlie the abnormal vascular cell proliferation observed in familial PAH. ..