{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T08:28:05Z","timestamp":1772958485958,"version":"3.50.1"},"reference-count":89,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2003,10,1]],"date-time":"2003-10-01T00:00:00Z","timestamp":1064966400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nat Rev Genet"],"published-print":{"date-parts":[[2003,10]]},"DOI":"10.1038\/nrg1178","type":"journal-article","created":{"date-parts":[[2003,10,3]],"date-time":"2003-10-03T12:50:25Z","timestamp":1065185425000},"page":"763-773","source":"Crossref","is-referenced-by-count":233,"title":["From developmental disorder to heritable cancer: it's all in the BMP\/TGF-\u03b2 family"],"prefix":"10.1038","volume":"4","author":[{"given":"Kristin A.","family":"Waite","sequence":"first","affiliation":[]},{"given":"Charis","family":"Eng","sequence":"additional","affiliation":[]}],"member":"297","reference":[{"key":"BFnrg1178_CR1","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1126\/science.7761852","volume":"268","author":"S Markowitz","year":"1995","unstructured":"Markowitz, S. et al. Inactivation of the type II TGF-B receptor in colon cancer cells with microsatellite instability. Science 268, 1336\u20131338 (1995).","journal-title":"Science"},{"key":"BFnrg1178_CR2","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1023\/A:1013177011767","volume":"20","author":"BA Teicher","year":"2001","unstructured":"Teicher, B. A. Malignant cells, directors of the malignant process: role of transforming growth factor-\u03b2. Cancer Met. Rev. 20, 133\u2013143 (2001).","journal-title":"Cancer Met. Rev."},{"key":"BFnrg1178_CR3","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1248\/bpb.23.1125","volume":"23","author":"K Miyazono","year":"2000","unstructured":"Miyazono, K. TGF-B\/SMAD signaling and its involvement in tumor progression. Biol. Pharm. Bull. 23, 1125\u20131130 (2000).","journal-title":"Biol. Pharm. Bull."},{"key":"BFnrg1178_CR4","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/S1359-6101(99)00025-8","volume":"11","author":"K Miyazono","year":"2000","unstructured":"Miyazono, K. TGF-B signaling by Smad proteins. Cytokine Growth Fact. Rev. 11, 15\u201322 (2000).","journal-title":"Cytokine Growth Fact. Rev."},{"key":"BFnrg1178_CR5","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/S0378-1119(00)00162-1","volume":"249","author":"CM Zimmerman","year":"2000","unstructured":"Zimmerman, C. M. & Padgett, R. W. Transforming growth factor-\u03b2 signaling mediators and modulators. Gene 249, 17\u201330 (2000).","journal-title":"Gene"},{"key":"BFnrg1178_CR6","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/ng1001-117","volume":"29","author":"R Derynck","year":"2001","unstructured":"Derynck, R., Akhurst, R. J. & Balmain, A. TGF-\u03b2 signaling in tumor suppression and cancer progression. Nature Genet. 29, 117\u2013129 (2001).","journal-title":"Nature Genet."},{"key":"BFnrg1178_CR7","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/S0092-8674(03)00432-X","volume":"113","author":"Y Shi","year":"2003","unstructured":"Shi, Y. & Massague, J. Mechanisms of TGF-\u03b2 signaling: from cell membrane to the nucleus. Cell 113, 685\u2013700 (2003).","journal-title":"Cell"},{"key":"BFnrg1178_CR8","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1038\/ng0397-277","volume":"15","author":"WC Nichols","year":"1997","unstructured":"Nichols, W. C. et al. Localization of the gene for familial primary pulmonary hypertension to chromosome 2q31-q33. Nature Genet. 15, 277\u2013280 (1997).","journal-title":"Nature Genet."},{"key":"BFnrg1178_CR9","doi-asserted-by":"crossref","first-page":"2603","DOI":"10.1161\/01.CIR.95.12.2603","volume":"95","author":"JH Morse","year":"1997","unstructured":"Morse, J. H. et al. Mapping of familial primary pulmonary hypertension locus (PPH1) to chromosome 2q31-q32. Circulation 95, 2603\u20132606 (1997).","journal-title":"Circulation"},{"key":"BFnrg1178_CR10","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1006\/geno.2000.6291","volume":"68","author":"RD Machado","year":"2000","unstructured":"Machado, R. D. et al. A physical and transcript map based upon refinement of the critical interval for PPH1, a gene for familial primary pulmonary hypertension. Genomics 68, 220\u2013228 (2000).","journal-title":"Genomics"},{"key":"BFnrg1178_CR11","doi-asserted-by":"crossref","unstructured":"International PPH Consortium. Heterozygous germline mutations in BMPR2, encoding a TGF\u03b2 receptor, cause familial primary pulmonary hypertension. Nature Genet. 26, 81\u201384 (2000). This study identifies BMPR2 as the susceptibility gene for familial primary pulmonary hypertension.","DOI":"10.1038\/79226"},{"key":"BFnrg1178_CR12","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1086\/303059","volume":"67","author":"Z Deng","year":"2000","unstructured":"Deng, Z. et al. Familial primary pulmonary hypertension (gene PPH1) is caused by mutations in the bone morphogenetic protein receptor-II gene. Am. J. Hum. Genet. 67, 737\u2013744 (2000).","journal-title":"Am. J. Hum. Genet."},{"key":"BFnrg1178_CR13","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1086\/316947","volume":"68","author":"RD Machado","year":"2001","unstructured":"Machado, R. D. et al. BMPR2 haploinsufficiency as the inherited molecular mechanism for primary pulmonary hypertension. Am. J. Hum. Genet. 68, 92\u2013102 (2001).","journal-title":"Am. J. Hum. Genet."},{"key":"BFnrg1178_CR14","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1136\/jmg.37.10.741","volume":"37","author":"JR Thomson","year":"2000","unstructured":"Thomson, J. R. et al. Sporadic primary pulmonary hypertension is associated with germline mutations of the gene encoding BMPR-II, a receptor member of the TGF-B family. J. Med. Genet. 37, 741\u2013745 (2000). This paper reports that \u223c25% of apparently sporadic cases of primary pulmonary hypertension carry unsuspected germline mutations in BMPR2.","journal-title":"J. Med. Genet."},{"key":"BFnrg1178_CR15","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1001\/jama.1996.03540190047028","volume":"276","author":"C Eng","year":"1996","unstructured":"Eng, C. et al. The relationship between specific RET proto-oncogene mutations and disease phenotype in multiple endocrine neoplasia type 2: International RET Mutation Consortium analysis. JAMA 276, 1575\u20131579 (1996).","journal-title":"JAMA"},{"key":"BFnrg1178_CR16","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1002\/(SICI)1097-4652(200007)184:1<37::AID-JCP4>3.0.CO;2-M","volume":"184","author":"H Dorai","year":"2000","unstructured":"Dorai, H., Vukecevic, S. & Sampath, T. K. Bone morphogenetic protein-7 (Op-1) inhibits smooth muscle cell proliferation and stimulates the expression of markers that are characteristic of SMC phenotype in vitro. J. Cell. Physiol. 184, 37\u201345 (2000).","journal-title":"J. Cell. Physiol."},{"key":"BFnrg1178_CR17","doi-asserted-by":"crossref","first-page":"2824","DOI":"10.1172\/JCI119830","volume":"100","author":"T Nakaoka","year":"1997","unstructured":"Nakaoka, T. et al. Inhibition of rat vascular smooth muscle proliferation in vitro and in vivo by morphogenetic protein-2. J. Clin. Invest. 100, 2824\u20132832 (1997).","journal-title":"J. Clin. Invest."},{"key":"BFnrg1178_CR18","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1161\/hc3201.094152","volume":"104","author":"NW Morrell","year":"2001","unstructured":"Morrell, N. W. et al. Altered growth responses of pulmonary artery smooth muscle cells from patients with primary pulmonary hypertension to transforming growth factor-B1 and bone morphogenetic proteins. Circulation 104, 790\u2013795 (2001).","journal-title":"Circulation"},{"key":"BFnrg1178_CR19","doi-asserted-by":"crossref","first-page":"1672","DOI":"10.1161\/01.CIR.0000012754.72951.3D","volume":"105","author":"C Atkinson","year":"2002","unstructured":"Atkinson, C. et al. Primary pulmonary hypertension is associated with reduced pulmonary vascular expression of type II bone morphogenetic protein receptor. Circulation 105, 1672\u20131678 (2002).","journal-title":"Circulation"},{"key":"BFnrg1178_CR20","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1093\/hmg\/11.13.1517","volume":"11","author":"N Rudarakanchana","year":"2002","unstructured":"Rudarakanchana, N. et al. Functional analysis of bone morphogenetic protein type II receptor mutations underlying primary pulmonary hypertension. Hum. Mol. Genet. 11, 1517\u20131525 (2002).","journal-title":"Hum. Mol. Genet."},{"key":"BFnrg1178_CR21","doi-asserted-by":"crossref","first-page":"3055","DOI":"10.1091\/mbc.e02-02-0063","volume":"13","author":"A Nishihara","year":"2002","unstructured":"Nishihara, A., Watabe, T., Imamura, T. & Miyazono, K. Functional heterogeneity of bone morphogenetic protein receptor-II mutants found in patients with primary pulmonary hypertension. Mol. Biol. Cell 13, 3055\u20133063 (2002).","journal-title":"Mol. Biol. Cell"},{"key":"BFnrg1178_CR22","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1038\/35043051","volume":"1","author":"J Massague","year":"2000","unstructured":"Massague, J. How cells read TGF-\u03b2 signals. Nature Rev. Mol. Cell. Biol. 1, 169\u2013178 (2000).","journal-title":"Nature Rev. Mol. Cell. Biol."},{"key":"BFnrg1178_CR23","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S1359-6101(01)00027-2","volume":"13","author":"AB Roberts","year":"2002","unstructured":"Roberts, A. B. The ever-increasing complexity of TGF-\u03b2 signaling. Cytokine Growth Fact. Rev. 13, 3\u20135 (2002).","journal-title":"Cytokine Growth Fact. Rev."},{"key":"BFnrg1178_CR24","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1038\/88802","volume":"28","author":"C Eng","year":"2001","unstructured":"Eng, C. To be or not to BMP. Nature Genet. 28, 105\u2013107 (2001).","journal-title":"Nature Genet."},{"key":"BFnrg1178_CR25","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1172\/JCI200112805","volume":"108","author":"S Eddahibi","year":"2001","unstructured":"Eddahibi, S. et al. Serotonin transporter overexpression is responsible for pulmonary artery smooth muscle hyperplasia in primary pulmonary hypertension. J. Clin. Invest. 108, 1141\u20131150 (2001).","journal-title":"J. Clin. Invest."},{"key":"BFnrg1178_CR26","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1136\/jmg.29.8.527","volume":"29","author":"MEM Porteus","year":"1992","unstructured":"Porteus, M. E. M., Burn, J. & Proctor, S. Hereditary haemorrhagic telangeictasia: a clinical analysis. J. Med. Genet. 29, 527\u2013530 (1992).","journal-title":"J. Med. Genet."},{"key":"BFnrg1178_CR27","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1056\/NEJM199510053331407","volume":"333","author":"AE Guttmacher","year":"1995","unstructured":"Guttmacher, A. E., Marchuk, D. A. & White, R. I. Hereditary hemorrhagic telangiectasia. N. Engl. J. Med. 333, 918\u2013924 (1995).","journal-title":"N. Engl. J. Med."},{"key":"BFnrg1178_CR28","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/0003-4975(94)91047-2","volume":"57","author":"RI White","year":"1994","unstructured":"White, R. I. & Pollak, J. S. Pulmonary arteriovenous malformations: options for management. Ann. Thorac. Surg. 57, 519\u2013521 (1994).","journal-title":"Ann. Thorac. Surg."},{"key":"BFnrg1178_CR29","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1038\/ng0294-205","volume":"6","author":"CL Shovlin","year":"1994","unstructured":"Shovlin, C. L. et al. A gene for hereditary haemorrhagic telangiectasia maps to chromosome 9q. Nature Genet. 6, 205\u2013209 (1994).","journal-title":"Nature Genet."},{"key":"BFnrg1178_CR30","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1093\/hmg\/4.5.945","volume":"4","author":"P Vincent","year":"1995","unstructured":"Vincent, P. et al. A third locus for hereditary haemorrhagic telangiectasia maps to chromosome 12q. Hum. Mol. Genet. 4, 945\u2013949 (1995).","journal-title":"Hum. Mol. Genet."},{"key":"BFnrg1178_CR31","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1101\/gr.5.1.21","volume":"5","author":"DW Johnson","year":"1995","unstructured":"Johnson, D. W. et al. A second locus for hereditary haemorrhagic telangiectasia maps to chromosome 12. Genome Res. 5, 21\u201328 (1995).","journal-title":"Genome Res."},{"key":"BFnrg1178_CR32","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/ng1294-345","volume":"8","author":"KA McAllister","year":"1994","unstructured":"McAllister, K. A. et al. Endoglin, a TGF-\u03b2 binding protein of endothelial cells, is the gene for hereditary haemorrhagic telangiectasia type 1. Nature Genet. 8, 345\u2013351 (1994). This study identifies ENG -encoding endoglin as a susceptibility gene for hereditary haemorrhagic telangiectasia.","journal-title":"Nature Genet."},{"key":"BFnrg1178_CR33","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1038\/ng0696-189","volume":"13","author":"DW Johnson","year":"1996","unstructured":"Johnson, D. W. et al. Mutations in the activin receptor-like kinase 1 gene in hereditary haemorrhagic telangiectasia type 2. Nature Genet. 13, 189\u2013196 (1996). In this study, ALK1 (ACVRL1 ) is identified as a second susceptibility gene for hereditary haemorrhagic telangiectasia.","journal-title":"Nature Genet."},{"key":"BFnrg1178_CR34","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1086\/513906","volume":"61","author":"CL Shovlin","year":"1997","unstructured":"Shovlin, C. L., Hughes, J. M. B., Scott, J., Seidman, C. E. & Seidman, J. G. Characterization of endoglin and identification of novel mutations in hereditary hemorrhagic telangiectasia. Am. J. Hum. Genet. 61, 68\u201379 (1997).","journal-title":"Am. J. Hum. Genet."},{"key":"BFnrg1178_CR35","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1136\/jmg.33.3.256","volume":"33","author":"JN Berg","year":"1996","unstructured":"Berg, J. N., Guttmacher, A. E., Marchuk, D. A. & Porteous, M. E. M. Clinical heterogeneity in hereditary haemorrhagic telangiectasia \u2014 are pulmonary arteriovenous malformations more common in families linked to endoglin? J. Med. Genet. 33, 256\u2013257 (1996).","journal-title":"J. Med. Genet."},{"key":"BFnrg1178_CR36","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1002\/humu.10026","volume":"19","author":"M Dakeishi","year":"2002","unstructured":"Dakeishi, M. et al. Genetic epidemiology of hereditary hemorrhagic telangiectasia in a local community in the northern part of Japan. Hum. Mutat. 19, 140\u2013148 (2002).","journal-title":"Hum. Mutat."},{"key":"BFnrg1178_CR37","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1007\/s004390000326","volume":"107","author":"CJ Gallione","year":"2000","unstructured":"Gallione, C. J. et al. Two common endoglin mutations in families with hereditary hemorrhagic telangiectasia in the Netherlands Antilles: evidence for a founder effect. Hum. Genet. 107, 40\u201344 (2000).","journal-title":"Hum. Genet."},{"key":"BFnrg1178_CR38","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1086\/513903","volume":"61","author":"JN Berg","year":"1997","unstructured":"Berg, J. N. et al. The activin receptor-like kinase 1 gene: genomic structure and mutations in hereditary hemorrhagic telangiectasia type 2. Am. J. Hum. Genet. 61, 60\u201367 (1997).","journal-title":"Am. J. Hum. Genet."},{"key":"BFnrg1178_CR39","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/sj.ejhg.5200919","volume":"11","author":"SA Abdalla","year":"2003","unstructured":"Abdalla, S. A., Cymerman, U., Johnson, R. M., Deber, C. M. & Letarte, M. Disease-associated mutations in conserved residues of ALK-1 kinase domain. Eur. J. Hum. Genet. 11, 279\u2013287 (2003).","journal-title":"Eur. J. Hum. Genet."},{"key":"BFnrg1178_CR40","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1126\/science.3291115","volume":"241","author":"SK Hanks","year":"1988","unstructured":"Hanks, S. K., Quinn, A. M. & Hunter, T. The protein kinase family: conserved features and deduced phylogeny of the catalytic domain. Science 241, 42\u201352 (1988).","journal-title":"Science"},{"key":"BFnrg1178_CR41","doi-asserted-by":"crossref","first-page":"2881","DOI":"10.1091\/mbc.12.9.2881","volume":"12","author":"N Garamszegi","year":"2001","unstructured":"Garamszegi, N. et al. Transforming growth factor-\u03b2 receptor signaling and endocytosis are linked through a COOH terminal activation motif in the type 1 receptor. Mol. Biol. Cell 12, 2881\u20132893 (2001).","journal-title":"Mol. Biol. Cell"},{"key":"BFnrg1178_CR42","doi-asserted-by":"crossref","first-page":"29197","DOI":"10.1074\/jbc.M111991200","volume":"277","author":"M Guerreoro-Esteo","year":"2002","unstructured":"Guerreoro-Esteo, M., Sanchez-Elsner, T., Letamendia, A. & Bernabeu, C. Extracellular and cytoplasmic domains of endoglin interact with the transforming growth factor-\u03b2 receptors I and II. J. Biol. Chem. 277, 29197\u201329209 (2002).","journal-title":"J. Biol. Chem."},{"key":"BFnrg1178_CR43","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1083\/jcb.133.5.1109","volume":"133","author":"P Lastres","year":"1996","unstructured":"Lastres, P. et al. Endoglin modulates cellular responses to TGF-\u03b21. J. Cell. Biol. 133, 1109\u20131121 (1996).","journal-title":"J. Cell. Biol."},{"key":"BFnrg1178_CR44","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1074\/jbc.274.2.584","volume":"274","author":"NP Barbara","year":"1999","unstructured":"Barbara, N. P., Wrana, J. L. & Letarte, M. Endoglin is an accessory protein that interacts with the signaling receptor complex of multiple members of the transforming growth factor B superfamily. J. Biol. Chem. 274, 584\u2013594 (1999).","journal-title":"J. Biol. Chem."},{"key":"BFnrg1178_CR45","doi-asserted-by":"crossref","first-page":"2568","DOI":"10.1172\/JCI119800","volume":"100","author":"S Pece","year":"1997","unstructured":"Pece, S. et al. Mutant endoglin in hereditary hemorrhagic telangiectasia type 1 is transiently expressed intracellularly and is not a dominant negative. J. Clin. Invest. 100, 2568\u20132579 (1997).","journal-title":"J. Clin. Invest."},{"key":"BFnrg1178_CR46","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1042\/bj3390579","volume":"339","author":"U Raab","year":"1999","unstructured":"Raab, U. et al. Expression of normal and truncated forms of human endoglin. Biochem. J. 339, 579\u2013588 (1999).","journal-title":"Biochem. J."},{"key":"BFnrg1178_CR47","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1093\/hmg\/9.5.745","volume":"22","author":"A Lux","year":"2000","unstructured":"Lux, A., Gallione, C. J. & Marchuk, D. A. Expression analysis of endoglin missense and truncation mutations: insights into protein structure and disease mechanisms. Hum. Mol. Genet. 22, 745\u2013755 (2000).","journal-title":"Hum. Mol. Genet."},{"key":"BFnrg1178_CR48","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1093\/hmg\/10.13.1347","volume":"10","author":"ME Paquet","year":"2001","unstructured":"Paquet, M. E. et al. Analysis of several endoglin mutants reveals no endogenous mature or secreted protein capable of interfering with normal endoglin function. Hum. Mol. Genet. 10, 1347\u20131357 (2001).","journal-title":"Hum. Mol. Genet."},{"key":"BFnrg1178_CR49","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1172\/JCI8088","volume":"104","author":"A Bourdeau","year":"1999","unstructured":"Bourdeau, A., Dumont, D. J. & Letarte, M. A. A murine model of hereditary hemorrhagic telangiectasia. J. Clin. Invest. 104, 1343\u20131351 (1999).","journal-title":"J. Clin. Invest."},{"key":"BFnrg1178_CR50","doi-asserted-by":"crossref","first-page":"2011","DOI":"10.1016\/S0002-9440(10)64673-1","volume":"158","author":"A Bourdeau","year":"2001","unstructured":"Bourdeau, A. et al. Potential role of modifier genes influencing transforming growth factor-B1 levels in the development of vascular defects in endoglin heterozygous mice with hereditary hemorrhagic telangiectasia. Am. J. Pathol. 158, 2011\u20132020 (2001).","journal-title":"Am. J. Pathol."},{"key":"BFnrg1178_CR51","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1161\/01.STR.0000056170.47815.37","volume":"34","author":"J Santomi","year":"2003","unstructured":"Santomi, J. et al. Cerebral vascular abnormalities in a murine model for hereditary hemorrhagic telangiectasia. Stroke 34, 783\u2013789 (2003).","journal-title":"Stroke"},{"key":"BFnrg1178_CR52","doi-asserted-by":"crossref","unstructured":"Fanning, A. S. & Anderson, J. M. Protein modules as organizers of membrane structure. Curr. Opin. Cell Biol. 432\u2013439 (1999).","DOI":"10.1016\/S0955-0674(99)80062-3"},{"key":"BFnrg1178_CR53","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1096\/fasebj.14.2.231","volume":"14","author":"BK Kay","year":"2000","unstructured":"Kay, B. K., Williamson, M. P. & Sudol, M. The importance of being proline: the interaction of proline-rich motifs in signaling proteins with their cognate domains. FASEB J. 14, 231\u2013241 (2000).","journal-title":"FASEB J."},{"key":"BFnrg1178_CR54","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1126\/science.280.5366.1086","volume":"280","author":"JR Howe","year":"1998","unstructured":"Howe, J. R. et al. Mutations in the SMAD4\/DPC4 gene in juvenile polyposis. Science 280, 1086\u20131088 (1998). This study identifies MADH4 as a susceptibility gene for a subset of families with juvenile polyposis syndrome.","journal-title":"Science"},{"key":"BFnrg1178_CR55","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1038\/88919","volume":"28","author":"JR Howe","year":"2001","unstructured":"Howe, J. R. et al. Germline mutations of BMPR1A in juvenile polyposis. Nature Genet. 28, 184\u2013187 (2001). In this study, BMPR1A germline mutations are identified in MADH4 -mutation negative probands with familial juvenile polyposis syndrome.","journal-title":"Nature Genet."},{"key":"BFnrg1178_CR56","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1086\/323703","volume":"69","author":"XP Zhou","year":"2001","unstructured":"Zhou, X. P. et al. Germline mutations in BMPR1A\/ALK3 cause a subset of juvenile polyposis syndrome and of Cowden and Bannayan\u2013Riley\u2013Ruvalcaba syndromes. Am. J. Hum. Genet. 69, 704\u2013711 (2001). This paper reports that germline BMPR1A mutations cause sporadic juvenile polyposis syndrome as well as rare Cowden syndrome probands.","journal-title":"Am. J. Hum. Genet."},{"key":"BFnrg1178_CR57","first-page":"165","volume":"1","author":"C Eng","year":"1988","unstructured":"Eng, C. & Blackstone, M. O. Peutz\u2013Jeghers syndrome. Med. Rounds 1, 165\u2013171 (1988).","journal-title":"Med. Rounds"},{"key":"BFnrg1178_CR58","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1136\/gut.25.7.792","volume":"25","author":"J Jarvinen","year":"1984","unstructured":"Jarvinen, J. & Franssila, K. O. Familial juvenile polyposis coli: increased risk of colorectal cancer. Gut 25, 792\u2013800 (1984).","journal-title":"Gut"},{"key":"BFnrg1178_CR59","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1007\/BF02306370","volume":"2","author":"MC Coburn","year":"1995","unstructured":"Coburn, M. C., Pricolo, V. E., DeLuca, F. G. & Bland, K. I. Malignant potential in intestinal juvenile polyposis syndromes. Ann. Surg. Oncol. 2, 386\u2013391 (1995).","journal-title":"Ann. Surg. Oncol."},{"key":"BFnrg1178_CR60","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1007\/BF02303487","volume":"5","author":"JR Howe","year":"1998","unstructured":"Howe, J. R., Mitros, F. A. & Summers, R. W. The risk of gastrointestinal carcinoma in familial juvenile polyposis. Ann. Surg. Oncol. 5, 751\u2013756 (1998).","journal-title":"Ann. Surg. Oncol."},{"key":"BFnrg1178_CR61","first-page":"107","volume":"23","author":"I Hofting","year":"1993","unstructured":"Hofting, I., Pott, G. & Stolte, M. Das syndrom der juvenilen polyposis. Leber Magen. Darm. 23, 107\u2013108 (1993).","journal-title":"Leber Magen. Darm."},{"key":"BFnrg1178_CR62","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1086\/340258","volume":"70","author":"JR Howe","year":"2002","unstructured":"Howe, J. R. et al. Common deletion of SMAD4 in juvenile polyposis is a mutational hotspot. Am. J. Hum. Genet. 70, 1357\u20131362 (2002).","journal-title":"Am. J. Hum. Genet."},{"key":"BFnrg1178_CR63","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1007\/s00439-002-0748-9","volume":"111","author":"W Friedl","year":"2002","unstructured":"Friedl, W. et al. Juvenile polyposis: massive gastric polyposis is more common in MADH4 mutation carriers than in BMPR1A mutation carriers. Hum. Genet. 111, 108\u2013111 (2002). This study shows that MADH4 -mutation positive juvenile polyposis probands are at increased risk of giant gastric polyps compared with those that have BMPR1A mutations.","journal-title":"Hum. Genet."},{"key":"BFnrg1178_CR64","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1007\/BF02557528","volume":"9","author":"MG Sayed","year":"2002","unstructured":"Sayed, M. G. et al. Germline SMAD4 or BMPR1A mutations and phenotype in juvenile polyposis. Ann. Surg. Oncol. 9, 901\u2013906 (2002).","journal-title":"Ann. Surg. Oncol."},{"key":"BFnrg1178_CR65","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1038\/40431","volume":"388","author":"Y Shi","year":"1997","unstructured":"Shi, Y., Hata, A., Lo, R. S., Massague, J. & Pavletich, N. P. A structural basis for the mutational inactivation of the tumor suppressor Smad4. Nature 388, 87\u201393 (1997).","journal-title":"Nature"},{"key":"BFnrg1178_CR66","doi-asserted-by":"crossref","first-page":"4056","DOI":"10.1093\/emboj\/17.14.4056","volume":"17","author":"M Kawabata","year":"1998","unstructured":"Kawabata, M., Inoue, H., Hanyu, A., Imamura, T. & Miyazono, K. SMAD proteins exist as monomers in vivo and undergo homo- and hetero-oligomerisation upon activation by serine\/threonine kinase receptors. EMBO J. 17, 4056\u20134065 (1998).","journal-title":"EMBO J."},{"key":"BFnrg1178_CR67","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1136\/gut.45.3.406","volume":"45","author":"S Bevan","year":"1999","unstructured":"Bevan, S. et al. Screening SMAD1, SMAD2, SMAD3 and SMAD5 for germline mutations in juvenile polyposis syndrome. Gut 45, 406\u2013408 (1999).","journal-title":"Gut"},{"key":"BFnrg1178_CR68","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1038\/ng0198-12","volume":"18","author":"S Olschwang","year":"1998","unstructured":"Olschwang, S., Serova-Sinilnikova, O. M., Lenoir, G. M. & Thomas, G. PTEN germline mutations in juvenile polyposis coli. Nature Genet. 18, 12\u201314 (1998).","journal-title":"Nature Genet."},{"key":"BFnrg1178_CR69","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1086\/301847","volume":"62","author":"C Eng","year":"1998","unstructured":"Eng, C. & Ji, H. Molecular classification of the inherited hamartoma polyposis syndromes: clearing the muddied waters. Am. J. Hum. Genet. 62, 1020\u20131022 (1998).","journal-title":"Am. J. Hum. Genet."},{"key":"BFnrg1178_CR70","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1086\/302207","volume":"64","author":"K Kurose","year":"1999","unstructured":"Kurose, K., Araki, T., Matsunaka, T., Takada, Y. & Emi, M. Variant manifestation of Cowden disease in Japan: hamartomatous polyposis of the digestive tract with mutation of the PTEN gene. Am. J. Hum. Genet. 64, 308\u2013310 (1999).","journal-title":"Am. J. Hum. Genet."},{"key":"BFnrg1178_CR71","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1136\/jmg.37.11.828","volume":"37","author":"C Eng","year":"2000","unstructured":"Eng, C. Will the real Cowden syndrome please stand up: revised diagnostic criteria. J. Med. Genet. 37, 828\u2013830 (2000).","journal-title":"J. Med. Genet."},{"key":"BFnrg1178_CR72","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1093\/hmg\/ddg069","volume":"12","author":"KA Waite","year":"2003","unstructured":"Waite, K. A. & Eng, C. BMP2 exposure results in decreased PTEN protein degradation leading to increased PTEN levels. Hum. Mol. Genet. 12, 679\u2013684 (2003). This study shows that BMP decreases PTEN protein degradation, which results in increased PTEN levels. Therefore, by implication, BMP signalling can result in apoptosis that is mediated by PTEN.","journal-title":"Hum. Mol. Genet."},{"key":"BFnrg1178_CR73","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1056\/NEJM200108023450503","volume":"345","author":"RC Trembath","year":"2001","unstructured":"Trembath, R. C. et al. Clinical and molecular genetic features of pulmonary hypertension in patients with hereditary hemorrhagic telangiectasia. N. Engl. J. Med. 345, 325\u2013334 (2001).","journal-title":"N. Engl. J. Med."},{"key":"BFnrg1178_CR74","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1002\/ajmg.1320390321","volume":"39","author":"V Blanquet","year":"1991","unstructured":"Blanquet, V., Cr\u00e9au-Goldberg, N., de Grouchy, J. & Turleau, C. Molecular detection of constitutional deletions in patients with retinoblastoma. Am. J. Med. Genet. 39, 355\u2013361 (1991).","journal-title":"Am. J. Med. Genet."},{"key":"BFnrg1178_CR75","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1093\/hmg\/4.3.383","volume":"4","author":"V Blanquet","year":"1995","unstructured":"Blanquet, V. et al. Spectrum of germline mutations in the RB1 gene: a study of 232 patients with hereditary and non hereditary retinoblastoma. Hum. Mol. Genet. 4, 383\u2013388 (1995).","journal-title":"Hum. Mol. Genet."},{"key":"BFnrg1178_CR76","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1002\/(SICI)1098-1004(1998)12:6<417::AID-HUMU8>3.0.CO;2-K","volume":"12","author":"C Stolle","year":"1998","unstructured":"Stolle, C. et al. Improved detection of germline mutations in the von Hippel-Lindau disease tumor suppressor gene. Hum. Mutat. 12, 417\u2013423 (1998).","journal-title":"Hum. Mutat."},{"key":"BFnrg1178_CR77","doi-asserted-by":"crossref","unstructured":"Zhou, X. P. et al. Germline PTEN promoter mutations and deletions in Cowden\/Bannayan\u2013Riley\u2013Ruvalcaba syndrome result in aberrant PTEN protein and dysregulation of the phosphoinositol-3-kinase\/Akt pathway. Am. J. Hum. Genet. (in the press).","DOI":"10.1086\/377109"},{"key":"BFnrg1178_CR78","doi-asserted-by":"crossref","first-page":"27","DOI":"10.3317\/jraas.2003.003","volume":"4","author":"WT Abraham","year":"2003","unstructured":"Abraham, W. T. et al. Angiotensin-converting enzyme DD genotype in patients with primary pulmonary hypertension: increased frequency and association with preserved haemodynamics. J. Renin Angiotens. Aldoster. Sys. 4, 27\u201330 (2003).","journal-title":"J. Renin Angiotens. Aldoster. Sys."},{"key":"BFnrg1178_CR79","first-page":"2902","volume":"114","author":"HC Weber","year":"1998","unstructured":"Weber, H. C., Marsh, D., Lubensky, I., Lin, A. & Eng, C. Germline PTEN\/MMAC1\/TEP1 mutations and association with gastrointestinal manifestations in Cowden disease. Gastroenterology 114, 2902 (1998).","journal-title":"Gastroenterology"},{"key":"BFnrg1178_CR80","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1038\/ng0197-87","volume":"15","author":"A Hemminki","year":"1997","unstructured":"Hemminki, A. et al. Localisation of a susceptibility locus for Peutz\u2013Jeghers syndrome to 19p using comparative genomic hybridization and targeted linkage analysis. Nature Genet. 15, 87\u201390 (1997).","journal-title":"Nature Genet."},{"key":"BFnrg1178_CR81","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1038\/34432","volume":"391","author":"A Hemminki","year":"1998","unstructured":"Hemminki, A. et al. A serine\/threonine kinase gene defective in Peutz\u2013Jeghers syndrome. Nature 391, 184\u2013187 (1998).","journal-title":"Nature"},{"key":"BFnrg1178_CR82","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1038\/ng0198-38","volume":"18","author":"DE Jenne","year":"1998","unstructured":"Jenne, D. E. et al. Peutz\u2013Jeghers syndrome is caused by mutations in a novel serine threonine kinase. Nature Genet. 18, 38\u201344 (1998).","journal-title":"Nature Genet."},{"key":"BFnrg1178_CR83","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1086\/301644","volume":"61","author":"H Mehenni","year":"1997","unstructured":"Mehenni, H. et al. Peutz\u2013Jeghers syndrome: confirmation of linkage to chromosome 19p13.3 and identification of a potential second locus on 19q13.4. Am. J. Hum. Genet. 61, 1327\u20131334 (1997).","journal-title":"Am. J. Hum. Genet."},{"key":"BFnrg1178_CR84","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1038\/ng0597-64","volume":"16","author":"D Liaw","year":"1997","unstructured":"Liaw, D. et al. Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome. Nature Genet. 16, 64\u201367 (1997).","journal-title":"Nature Genet."},{"key":"BFnrg1178_CR85","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1093\/hmg\/7.3.507","volume":"7","author":"DJ Marsh","year":"1998","unstructured":"Marsh, D. J. et al. Mutation spectrum and genotype\u2013phenotype analyses in Cowden disease and Bannayan\u2013Zonana syndrome, two hamartoma syndromes with germline PTEN mutation. Hum. Mol. Genet. 7, 507\u2013515 (1998).","journal-title":"Hum. Mol. Genet."},{"key":"BFnrg1178_CR86","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/ng0897-333","volume":"16","author":"DJ Marsh","year":"1997","unstructured":"Marsh, D. J. et al. Germline mutations in PTEN are present in Bannayan\u2013Zonana syndrome. Nature Genet. 16, 333\u2013334 (1997).","journal-title":"Nature Genet."},{"key":"BFnrg1178_CR87","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1093\/hmg\/8.8.1461","volume":"8","author":"DJ Marsh","year":"1999","unstructured":"Marsh, D. J. et al. PTEN mutation spectrum and genotype\u2013phenotype correlations in Bannayan\u2013Riley\u2013Ruvalcaba syndrome suggest a single entity with Cowden syndrome. Hum. Mol. Genet. 8, 1461\u20131472 (1999).","journal-title":"Hum. Mol. Genet."},{"key":"BFnrg1178_CR88","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1086\/375144","volume":"72","author":"EEM Jaeger","year":"2003","unstructured":"Jaeger, E. E. M. et al. An ancestral Ashkenazi haplotype at the HMPS\/CRAC1 locus on 15q13-q14 is associated with hereditary mixed polyposis syndrome. Am. J. Hum. Genet. 72, 1261\u20131267 (2003).","journal-title":"Am. J. Hum. Genet."},{"key":"BFnrg1178_CR89","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/S0008-6363(02)00852-0","volume":"58","author":"S van den Driesche","year":"2003","unstructured":"van den Driesche, S., Mummery, C. L. & Westermann, C. J. Hereditary hemorrhagic telangiectasia: an update on transforming growth factor-\u03b2 signaling in vasculogenesis and angiogenesis. Cardiovasc. Res. 58, 20\u201331 (2003).","journal-title":"Cardiovasc. Res."}],"container-title":["Nature Reviews Genetics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/nrg1178","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nrg1178.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nrg1178.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,19]],"date-time":"2023-05-19T03:56:21Z","timestamp":1684468581000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/nrg1178"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,10]]},"references-count":89,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2003,10]]}},"alternative-id":["BFnrg1178"],"URL":"https:\/\/doi.org\/10.1038\/nrg1178","relation":{},"ISSN":["1471-0056","1471-0064"],"issn-type":[{"value":"1471-0056","type":"print"},{"value":"1471-0064","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,10]]}}}