TGF-β signalling from cell membrane to nucleus through SMAD proteins (original) (raw)
Massagué, J., Hata, A. & Liu, F. TGF- β signalling through the Smad pathway. Trends Cell Biol.7, 187 –192 (1997). Article Google Scholar
Wrana, J. L., Attisano, L., Wieser, R., Ventura, F. & Massagué, J. Mechanism of activation of the TGF- β receptor. Nature370, 341 –347 (1994). ArticleADSCASPubMed Google Scholar
Henis, Y. I., Moustakas, A., Lin, H. Y. & Lodish, H. F. The types II and III transforming growth factor- β receptors form homo-oligomers. J. Cell Biol.126, 139 –154 (1994). ArticleCASPubMed Google Scholar
Chen, R.-H. & Derynck, R. Homomeric interactions between type II transforming growth factor- β receptors. J. Biol. Chem.269, 22868 –22874 (1994). CASPubMed Google Scholar
Lu, K. X. & Lodish, H. F. Signalling by chimeric erythropoietin-TGF- β receptors: Homodimerization of the cytoplasmic domain of the type I TGF- β receptor and heterodimerization with the type II receptor are both required for intracellular signal transduction. EMBO J.15, 4485 –4496 (1996). Article Google Scholar
Feng, X.-H. & Derynck, R. Ligand-independent activation of transforming growth factor (TGF) β signaling pathways by heteromeric cytoplasmic domains of TGF- β receptors. J. Biol. Chem.271, 13123 –13129 (1996). ArticleCASPubMed Google Scholar
Wieser, R., Wrana, J. L. & Massagué, J. GS domain mutations that constitutively activate T βR-I, the downstream signaling component in the TGF- β receptor complex. EMBO J.14, 2199 –2208 (1995). ArticleCASPubMedPubMed Central Google Scholar
Attisano, L., Wrana, J. L., Montalvo, E. & Massagué, J. Activation of signalling by the activin receptor complex. Mol. Cell. Biol.16, 1066 –1073 (1996). ArticleCASPubMedPubMed Central Google Scholar
Willis, S. A., Zimmerman, C. M., Li, L. & Mathews, L. S. Formation and activation by phosphorylation of activin receptor complexes. Mol. Endocrinol.10, 367 –379 (1996). CASPubMed Google Scholar
Rodriguez, C., Chen, F., Weinberg, R. A. & Lodish, H. F. Cooperative binding of transforming growth factor (TGF)- β2 to the types I and II TGF- β receptors. J. Biol. Chem.270, 15919 –15922 (1995). ArticleCASPubMed Google Scholar
Liu, F., Ventura, F., Doody, J. & Massagué, J. Human type II receptor for bone morphogenic proteins (BMPs): Extension of the two-kinase receptor model to the BMPs. Mol. Cell. Biol.15, 3479 –3486 (1995). ArticleCASPubMedPubMed Central Google Scholar
Nohno, T. et al. Identification of a human type Ii receptor for bone morphogenetic protein-4 that forms differential heteromeric complexes with bone morphogenetic protein type I receptors. J. Biol. Chem.270, 22522 –22526 (1995). ArticleCASPubMed Google Scholar
Rosenzweig, B. L. et al. Cloning and characterization of a human type II receptor for bone morphogenetic proteins. Proc. Natl Acad. Sci. USA92, 7632 –7636 (1995). ArticleADSCASPubMedPubMed Central Google Scholar
Yamashita, H., ten Dijke, P., Franzén, P., Miyazono, K. & Heldin, C.-H. Formation of hetero-oligomeric complexes of type I and type II receptors for transforming growth factor- β. J. Biol. Chem.269, 20172 –20178 (1994). CASPubMed Google Scholar
Weis-Garcia, F. & Massagué, J. Complementation between kinase-defective and activation-defective TGF- β receptors reveals a novel form of receptor cooperativity essential for signaling. EMBO J.15, 276 –289 (1996). ArticleCASPubMedPubMed Central Google Scholar
C árcamo, J. et al. Type I receptors specify growth-inhibitory and transcriptional responses to transforming growth factor beta and activin. Mol. Cell. Biol.14, 3810 –3821 (1994). Article Google Scholar
Feng, X.-H. & Derynck, R. Akinase subdomain of transforming growth factor- β (TGF- β) type I receptor determines the TGF- β intracellular signaling specificity. EMBO J.16, 3912 –3923 (1997). ArticleCASPubMedPubMed Central Google Scholar
McCaffrey, T. A. et al. Decreased type II/type I TGF- β receptor ratio in cells derived from human atherosclerotic lesions. Conversion from an antiproliferative to profibrotic response to TGF- β1. J. Clin. Invest.96, 2667 –2675 (1995). ArticleCASPubMedPubMed Central Google Scholar
Sankar, S. et al. Modulation of transforming growth factor β receptor levels on microvascular endothelial cells during in vitro angiogenesis. J. Clin. Invest.97, 1436 –1446 (1996). ArticleCASPubMedPubMed Central Google Scholar
Chen, R. H., Ebner, R. & Derynck, R. Inactivation of the type II receptor reveals two receptor pathways for the diverse TGF- β activities. Science260, 1335 –1338 (1993). ArticleADSCASPubMed Google Scholar
Souchelnytskyi, S., ten Dijke, P., Miyazono, K. & Heldin, C.-H. Phosphorylation of Ser165 in TGF- β type I receptor modulates TGF- β1-induced cellular responses. EMBO J.15, 6231 –6240 (1996). ArticleCASPubMedPubMed Central Google Scholar
Luo, K. X. & Lodish, H. F. Positive and negative regulation of type II TGF β receptor signal transduction by autophosphorylation on multiple serine residues. EMBO J.16, 1970 –1981 (1997). ArticleCASPubMedPubMed Central Google Scholar
Lawler, S. et al. The type II transforming growth factor- β receptor autophosphoryltes not only on serine and threonine but also on tyrosine residues. J. Biol. Chem.272, 14850 –14859 (1997). ArticleCASPubMed Google Scholar
Nakamura, T. et al. Isolation and characterization of activin receptor from mouse embryonal carcinoma cells: Identification of its serine/threonine/tyrosine protein kinase activity. J. Biol. Chem.267, 18924 –18928 (1992). CASPubMed Google Scholar
Raftery, L. A., Twombly, V., Wharton, K. & Gelbart, W. M. Genetic screens to identify elements of the decapentaplegic signaling pathway in Drosophila. Genetics139, 241 –254 (1995). CASPubMedPubMed Central Google Scholar
Sekelsky, J. J., Newfeld, S. J., Raftery, L. A., Chartoff, E. H. & Gelbart, W. M. Genetic characterization and cloning of Mothers against dpp, a gene required for decapentaplegic function in Drosophila melanogaster. Genetics139, 1347 –1358 (1995). CASPubMedPubMed Central Google Scholar
Wiersdorff, V., Lecuit, T., Cohen, S. M. & Mlodzik, M. Mad acts downstream of Dpp receptors, revealing a differential requirement for dpp signaling in initiation and propagation of morphogenesis in the Drosophila eye. Development122, 2153 –2162 (1996). CASPubMed Google Scholar
Newfeld, S. J., Chartoff, E. H., Graff, J. M., Melton, D. A. & Gelbart, W. M. Mothers against dpp encodes a conserved cytoplasmic protein required in DPP/TGF- β responsiveness cells. Development122, 2099 –2108 (1996). CASPubMed Google Scholar
Hoodless, P. A. et al. MADR1, a MAD-related protein that functions in BMP2 signaling pathways. Cell85, 489 –500 (1996). ArticleCASPubMed Google Scholar
Newfeld, S. J. et al. Mothers against dpp participates in a DPP/TGF- β responsive serine –threonine kinase signal transduction cascade. Development124, 3167 –3176 (1997). CASPubMed Google Scholar
Savage, C. et al. Caenorhabditis elegans genes sma-2, sma-3, and sma-4 define a conserved family of transforming growth factor β pathway components. Proc. Natl Acad. Sci. USA93, 790 –794 (1996). ArticleADSCASPubMedPubMed Central Google Scholar
Graff, J. M., Bansal, A. & Melton, D. A. Xenopus Mad proteins transduce distinct subsets of signals for the TGF β superfamily. Cell85, 479 –487 (1996). ArticleCASPubMed Google Scholar
Thomsen, G. H. Xenopus mothers against decapentaplegic is an embryonic ventralizing agent that acts downstream of the BMP-2/4 receptor. Development122, 2359 –2366 (1996). CASPubMed Google Scholar
Liu, F. et al. Ahuman Mad protein acting as a BMP-regulated transcriptional activator. Nature381, 620 –623 (1996). ArticleADSCASPubMed Google Scholar
Baker, J. C. & Harland, R. M. Anovel mesoderm inducer, Madr2, functions in the activin signal transduction pathway. Genes Dev.10, 1880 –1889 (1996). ArticleCASPubMed Google Scholar
Eppert, K. et al. MADR2 maps to 18q21 and encodes a TGF β-regulated MAD-related protein that is functionally mutated in colorectal carcinoma. Cell86, 543 –552 (1996). ArticleCASPubMed Google Scholar
Zhang, Y., Feng, X.-H., Wu, R.-Y. & Derynck, R. Receptor-associated Mad homologues synergize as effectors of the TGF- β response. Nature383, 168 –172 (1996). ArticleADSCASPubMed Google Scholar
Chen, Y., Lebrun, J. J. & Vale, W. Regulation of transforming growth factor β- and activin-induced transcription by mammalian Mad proteins. Proc. Natl Acad. Sci. USA93, 12992 –12997 (1996). ArticleADSCASPubMedPubMed Central Google Scholar
Kretzschmar, M., Liu, F., Hata, A., Doody, J. & Massagué, J. The TGF- β family mediator Smad1 is phosphorylated directly and activated functionally by the BMP receptor kinase. Genes Dev.11, 984 –995 (1997). ArticleCASPubMed Google Scholar
Suzuki, A., Chang, C., Yingling, J. M., Wang, X.-F. & Hemmati-Brivvanlous, A. Smad5 induces ventral fates in Xenopus embryo. Dev. Biol.184, 402 –405 (1997). ArticleCASPubMed Google Scholar
Watanabe, T. K. et al. Cloning and characterization of a novel member of the human Mad gene family. Genomics42, 446 –451 (1997). ArticleCASPubMed Google Scholar
Lechleider, R. J., de Caestecker, M. P., Dehejia, A., Polymeropoulos, M. H. & Roberts, A. B. Serine phosphorylation, chroosomal localization, and transforming growth factor- β signal transduction by human bsp-1. J. Biol. Chem.271, 17617 –17620 (1996). ArticleCASPubMed Google Scholar
Yingling, J. M. et al. Mammalian dwarfins are phosphorylated in response to transforming growth factor β and are implicated in control of cell growth. Proc. Natl Acad. Sci. USA93, 8940 –8944 (1996). ArticleADSCASPubMedPubMed Central Google Scholar
Marc ías-Silva, M. et al. MADR2 is a substrate of the TGF β receptor and its phosphorylation is required for nuclear accumulation and signaling. Cell87, 1215 –1224 (1996). Article Google Scholar
Souchelnytskyi, S. et al. Phosphorylation of Ser465 and Ser467 in the C-terminus of Smad2 mediates interaction with Smad4 and is required for TGF- β signalling. J. Biol. Chem.272, 28107 –28115 (1997). ArticleCASPubMed Google Scholar
Abdollah, S. et al. T βRI phosphorylation of Smad2 on Ser465 and 467 is required for Smad2/Smad4 complex formation and signalling. J. Biol. Chem.272, 27678 –27685 (1997). ArticleCASPubMed Google Scholar
Lagna, G., Hata, A., Hammati-Brivanlou, A. & Massagué, J. Partnership between DPC4 and SMAD proteins in TGF- β signalling pathways. Nature383, 832 –836 (1996). ArticleADSCASPubMed Google Scholar
Wu, R.-Y., Zhang, Y., Feng, X.-Y. & Derynck, R. Heteromeric and homomeric interactions correlate with signaling activity and functional cooperativity of Smad3 and Smad4/DPC4. Mol. Cell. Biol.17, 2521 –2528 (1997). ArticleCASPubMedPubMed Central Google Scholar
Zhang, Y., Musci, T. & Derynck, R. The tumor suppressor Smad4/DPC4 as a central mediator of Smad function. Curr. Biol.7, 270 –276 (1997). ArticlePubMed Google Scholar
Padgett, R. W., Savage, C. & Das, P. Genetic and biochemical analysis of TGF β signal transduction. Cytokine Growth Factor Rev.8, 1 –9 (1997). ArticleCASPubMed Google Scholar
de Caestecker, M. P. et al. Characterization of functional domains within smad4/DPC4. J. Biol. Chem.272, 13690 –13696 (1997). ArticleCASPubMed Google Scholar
Meersseman, G. et al. The C-terminal domain of Mad-like signal transducers is sufficient for biological activity in the Xenopus embryo and transcriptional activation. Mech. Dev.61, 127 –140 (1997). ArticleCASPubMed Google Scholar
Hata, A., Lo, R. S., Wotton, D., Lagna, G. & Massagué, J. Mutations increasing autoinhibition inactivate tumour suppressors Smad2 and Smad4. Nature388, 82 –87 (1997). ArticleADSCASPubMed Google Scholar
Schutte, M. et al. DPC4 gene in various tumour types. Cancer Res.56, 2527 –2530 (1996). CASPubMed Google Scholar
Kim, J., Johnson, K., Chen, H. J., Carroll, S. & Laughon, A. Drosophila Mad binds to DNA and directly mediates activation of vestigial by Decapentaplegic. Nature388, 304 –308 (1997). ArticleADSCASPubMed Google Scholar
Shi, Y., Hata, A., Lo, R. S., Massagué, J. & Pavletich, N. P. Astructural basis for mutational inactivation of the tumour suppressor Smad4. Nature388, 87 –93 (1997). ArticleADSCASPubMed Google Scholar
Imamura, T. et al. Smad6 is an inhibitor in the TGF- β superfamily signalling. Nature389, 622 –626 (1997). ArticleADSCASPubMed Google Scholar
Nakao, A. et al. Identification of Smad7, a TGF- β-inducible antagonist of TGF- β signalling. Nature389, 631 –635 (1997). ArticleADSCASPubMed Google Scholar
Hayashi, H. et al. The MAD-related protein Smad7 associates with the TGF β receptor and functions as an antagonist of TGF β signaling. Cell89, 1165 –1173 (1997). ArticleCASPubMed Google Scholar
Topper, J. N. et al. Vascular MAD s: Two novel MAD -related genes selectively inducible by flow in human vascular endothelium. Proc. Natl Acad. Sci. USA94, 9314 –9319 (1997). ArticleADSCASPubMedPubMed Central Google Scholar
Tsuneizumi, K. et al. Daughters against dpp modulates dpp organizing activity in Drosophila wing development. Nature389, 627 –631 (1997). ArticleADSCASPubMed Google Scholar
Watabe, T. et al. Molecular mechanisms of Spemann's organizer formation: conserved growth factor synergy between Xenopus and mouse. Genes Dev.9, 3038 –3050 (1995). ArticleCASPubMed Google Scholar
Kaufmann, E. et al. Antagonistic actions of activin A and BMP-2/4 control dorsal lip-specific activation of the early response gene XFD-1 ′ in Xenopus laevis embryos. EMBO J.15, 6739 –6749 (1996). ArticleCASPubMedPubMed Central Google Scholar
Ladher, R., Mohun, T. J., Smith, J. C. & Snape, A. M. Xom : a Xenopus homeobox gene that mediates the early effects of BMP-4. Development122, 2385 –2394 (1996). CASPubMed Google Scholar
Gawantka, V., Delius, H., Hirschfeld, K., Blumenstock, C. & Niehrs, C. Antagonizing the Spemann organizer: role of the homeobox gene Xvent-1. EMBO J.14, 6268 –6279 (1995). ArticleCASPubMedPubMed Central Google Scholar
Suzuki, A., Ueno, N. & Hemmati-Brivvanlou, A. Xenopus msx1 mediates epidermal induction and neural inhibition by BMP4. Development124, 3037 –3044 (1997). CASPubMed Google Scholar
Keeton, M. R., Curriden, S. A., van Zonneveld, A. J. & Loskutoff, D. J. Identification of regulatory sequences in the type I plasminogen activator inhibitor gene responsive to transforming growth factor β. J. Biol. Chem.266, 23048 –23052 (1991). CASPubMed Google Scholar
Kim, S. J. et al. Autoinduction of transforming growth factor β1 is mediated by the AP-1 complex. Mol. Cell. Biol.10, 1492 –1497 (1990). ArticleCASPubMedPubMed Central Google Scholar
Datto, M. B., Yu, Y. & Wang, X.-F. Functional analysis of the transforming growth factor β responsive elements in the WAF1/Cip1/p21 promoter. J. Biol. Chem.270, 28623 –28628 (1995). ArticleCASPubMed Google Scholar
Li, J.-M., Nichols, M. A., Chandrasekharan, S., Xiong, Y. & Wang, X.-F. Transforming growth factor β activates the promoter of cyclin-dependent kinase inhibitor p15_INK4B_ through an Sp1 consensus site. J. Biol. Chem.270, 26750 –26753 (1995). ArticleCASPubMed Google Scholar
Chen, X., Rubock, M. J. & Whitman, M. Atranscriptional partner for MAD proteins in TGF- β signalling. Nature383, 691 –696 (1996). ArticleADSCASPubMed Google Scholar
Chen, X. et al. Smad4 and FAST-1 in the assembly of activin-responsive factor. Nature389, 85 –89 (1997). ArticleADSCASPubMed Google Scholar
Arora, K. et al. The Drosophila schnurri gene acts in the Dpp/TGF- β signaling pathway and encodes a transcription factor homologous to the human MBP family. Cell81, 781 –790 (1995). ArticleCASPubMed Google Scholar
Grieder, N. C., Nellen, D., Burke, R., Basler, K. & Affolter, M. schnurri is required for Drosophila Dpp signaling and encodes a zinc finger protein similar to the mammalian transcription factor PRDII-BF1. Cell81, 791 –800 (1995). ArticleCASPubMed Google Scholar
Wilson, P. A., Lagna, G., Suzuki, A. & Hemmati-Brivvanlou, A. Concentration-dependent patterning of the Xenopus ectoderm by BMP4 and its signal transducer Smad1. Development124, 3177 –3184 (1997). CASPubMed Google Scholar
Charng, M.-J., Kinnunen, P., Hawker, J., Brand, T. & Schneider, M. D. FKBP-12 recognition is dispensable for signal generation by type I transforming growth factor- β receptors. J. Biol. Chem.271, 22941 –22944 (1996). ArticleCASPubMed Google Scholar
Wang, T. et al. The immunophilin FKBP12 functions as a common inhibitor of the TGF β family type I receptors. Cell86, 435 –444 (1996). ArticleCASPubMed Google Scholar
Kawabata, M., Imamura, T., Miyazono, K., Engel, M. E. & Moses, H. L. Interaction of the transforming growth factor- β type I receptor with farnesyl-protein transferase- α. J. Biol. Chem.270, 29628 –29631 (1995). ArticleCASPubMed Google Scholar
Ventura, F., Liu, F., Doody, J. & Massagué, J. Interaction of transforming growth factor- β receptor I with farnesyl-protein transferase- α in yeast and mammalian cells. J. Biol. Chem.271, 13931 –13934 (1996). ArticleCASPubMed Google Scholar
Wang, T. et al. The p21RAS farnesyltransferase α subunit in TGF- β and activin signaling. Science271, 1120 –1122 (1996). ArticleADSCASPubMed Google Scholar
Reddy, K. B., Karode, M. C., Harmony, J. A. K. & Howe, P. H. Interaction of transforming growth factor β receptors with apolipoprotein J/clusterin. Biochemistry35, 309 –314 (1996). ArticleCASPubMed Google Scholar
Chen, R.-H., Miettinen, P. J., Maruoka, E. M., Choy, L. & Derynck, R. AWD-domain protein that is associated with and phosphorylated by the type II TGF- β receptor. Nature377, 548 –552 (1995). ArticleADSCASPubMed Google Scholar
Yamaguchi, K. et al. Identification of a member of the MAPKKK family as a potential mediator of TGF- β signal transduction. Science270, 2008 –2011 (1995). ArticleADSCASPubMed Google Scholar
Hartsough, M. T. et al. Altered transforming growth factor β signaling in epithelial cells when Ras activation is blocked. J. Biol. Chem.271, 22368 –22375 (1996). ArticleCASPubMed Google Scholar
Mucsi, I., Skorecki, K. L. & Goldberg, H. J. Extracellular signal-regulated kinase and the small GTP-binding protein, Rac, contribute to the effects of transforming growth factor- β1 on gene expression. J. Biol. Chem.271, 16567 –16572 (1996). ArticleCASPubMed Google Scholar
Atfi, A., Djelloul, S., Chastre, E., Davis, R. R. & Gespach, C. Evidence for a role of Rho-like GTPases and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) in transforming growth factor beta-mediated signaling. J. Biol. Chem.272, 1429 –1432 (1997). ArticleCASPubMed Google Scholar
Frey, R. S. & Mulder, K. M. Involvement of extracellular signal-regulated kinase 2 and stress-activated protein kinase Jun N-terminal kinase activation by transforming growth factor β in the negative growth control of breast cancer cells. Cancer Res.57, 628 –633 (1997). CASPubMed Google Scholar
Cui, W. et al. TGF β1 inhibits the formation of benign skin tumors, but enhances progression to invasive spindle carcinomas in transgenic mice. Cell86, 531 –542 (1996). ArticleCASPubMed Google Scholar
Markowitz, S. D. & Roberts, A. B. Tumor suppressor activity of the TGF- β pathway in human cancers. Cytokine & Growth Factor Rev.7, 93 –102 (1996). ArticleCAS Google Scholar
Markowitz, S. et al. Inactivation of the type II TGF- β receptor in colon cancer cells with microsatellite instability. Science268, 1336 –1338 (1995). ArticleADSCASPubMed Google Scholar
Hahn, S. A. et al. DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1. Science271, 350 –353 (1996). ArticleADSCASPubMed Google Scholar
Riggins, R. G., Kinzler, K. W., Vogelstein, B. & Thiagalingamm, S. Frequency of Smad gene mutations in human cancers. Cancer Res.57, 2578 –2580 (1997). CASPubMed Google Scholar
Hannon, G. J. & Beach, D. p15INK4B is a potential effector of TGF- β-induced cell-cycle arrest. Nature371, 257 –261 (1994). ArticleADSCASPubMed Google Scholar
Iavarone, A. & Massagué, J. Repression of the CDK activator Cdc25A and cell-cycle arrest by cytokine TGF- β in cells lacking the CDK inhibitor p15. Nature387, 417 –422 (1997). ArticleADSCASPubMed Google Scholar
Galaktionov, K., Chen, X. & Beach, D. Cdc25 cell-cycle phosphatase as a target of c-Myc. Nature382, 511 –517 (1996). ArticleADSCASPubMed Google Scholar
Pietenpol, J. A. et al. TGF- β1 inhibition of c-myc transcription and growth in keratinocytes is abrogated by viral transforming proteins with pRB binding domains. Cell61, 777 –785 (1990). ArticleCASPubMed Google Scholar
Ihle, J. N. STATs: Signal transducers and activators of transcription. Cell84, 331 –334 (1996). ArticleCASPubMed Google Scholar
Kretzschmar, M., Doody, J. & Massagué, J. Opposing BMP and EGF signalling pathways converge on the TGF- β family mediator Smad1. Nature389, 618 –622 (1997). ArticleADSCASPubMed Google Scholar