Regulation of the Polarity Protein Par6 by TGFβ Receptors Controls Epithelial Cell Plasticity
The transition of cells from an epithelial to a mesenchymal phenotype is a critical event during morphogenesis in multicellular organisms and underlies the pathology of many diseases, including the invasive phenotype associated with metastatic carcinomas. Transforming growth factor β (TGFβ) is a key...
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| Veröffentlicht in: | Science (American Association for the Advancement of Science) 2005-03, Vol.307 (5715), p.1603-1609 |
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| container_title | Science (American Association for the Advancement of Science) |
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| creator | Ozdamar, Barish Bose, Rohit Barrios-Rodiles, Miriam Wang, Hong-Rui Zhang, Yue Wrana, Jeffrey L. |
| description | The transition of cells from an epithelial to a mesenchymal phenotype is a critical event during morphogenesis in multicellular organisms and underlies the pathology of many diseases, including the invasive phenotype associated with metastatic carcinomas. Transforming growth factor β (TGFβ) is a key regulator of epithelial-to-mesenchymal transition (EMT). However, the molecular mechanisms that control the dissolution of tight junctions, an early event in EMT, remain elusive. We demonstrate that Par6, a regulator of epithelial cell polarity and tight-junction assembly, interacts with TGFβ receptors and is a substrate of the type II receptor, TβRII. Phosphorylation of Par6 is required for TGFβ-dependent EMT in mammary gland epithelial cells and controls the interaction of Par6 with the E3 ubiquitin ligase Smurf1. Smurf1, in turn, targets the guanosine triphosphatase RhoA for degradation, thereby leading to a loss of tight junctions. These studies define how an extracellular cue signals to the polarity machinery to control epithelial cell morphology. |
| doi_str_mv | 10.1126/science.1105718 |
| format | Article |
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Transforming growth factor β (TGFβ) is a key regulator of epithelial-to-mesenchymal transition (EMT). However, the molecular mechanisms that control the dissolution of tight junctions, an early event in EMT, remain elusive. We demonstrate that Par6, a regulator of epithelial cell polarity and tight-junction assembly, interacts with TGFβ receptors and is a substrate of the type II receptor, TβRII. Phosphorylation of Par6 is required for TGFβ-dependent EMT in mammary gland epithelial cells and controls the interaction of Par6 with the E3 ubiquitin ligase Smurf1. Smurf1, in turn, targets the guanosine triphosphatase RhoA for degradation, thereby leading to a loss of tight junctions. These studies define how an extracellular cue signals to the polarity machinery to control epithelial cell morphology.</description><identifier>ISSN: 0036-8075</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.1105718</identifier><identifier>CODEN: SCIEAS</identifier><language>eng</language><publisher>Washington, DC: American Association for the Advancement of Science</publisher><subject>Analysis ; Biological and medical sciences ; Cancer ; Care and treatment ; Cell lines ; Cell physiology ; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes ; Epithelial cells ; Fundamental and applied biological sciences. Psychology ; Gene expression regulation ; Immunoblotting ; Immunoprecipitation ; Molecular and cellular biology ; Observations ; Phenotypes ; Phosphorylation ; Proteins ; Receptors ; Small interfering RNA ; Tight junctions</subject><ispartof>Science (American Association for the Advancement of Science), 2005-03, Vol.307 (5715), p.1603-1609</ispartof><rights>Copyright 2005 American Association for the Advancement of Science</rights><rights>2005 INIST-CNRS</rights><rights>COPYRIGHT 2005 American Association for the Advancement of Science</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/3841771$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/3841771$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>314,780,784,803,27924,27925,58017,58250</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16618567$$DView record in Pascal Francis$$Hfree_for_read</backlink></links><search><creatorcontrib>Ozdamar, Barish</creatorcontrib><creatorcontrib>Bose, Rohit</creatorcontrib><creatorcontrib>Barrios-Rodiles, Miriam</creatorcontrib><creatorcontrib>Wang, Hong-Rui</creatorcontrib><creatorcontrib>Zhang, Yue</creatorcontrib><creatorcontrib>Wrana, Jeffrey L.</creatorcontrib><title>Regulation of the Polarity Protein Par6 by TGFβ Receptors Controls Epithelial Cell Plasticity</title><title>Science (American Association for the Advancement of Science)</title><description>The transition of cells from an epithelial to a mesenchymal phenotype is a critical event during morphogenesis in multicellular organisms and underlies the pathology of many diseases, including the invasive phenotype associated with metastatic carcinomas. Transforming growth factor β (TGFβ) is a key regulator of epithelial-to-mesenchymal transition (EMT). However, the molecular mechanisms that control the dissolution of tight junctions, an early event in EMT, remain elusive. We demonstrate that Par6, a regulator of epithelial cell polarity and tight-junction assembly, interacts with TGFβ receptors and is a substrate of the type II receptor, TβRII. Phosphorylation of Par6 is required for TGFβ-dependent EMT in mammary gland epithelial cells and controls the interaction of Par6 with the E3 ubiquitin ligase Smurf1. Smurf1, in turn, targets the guanosine triphosphatase RhoA for degradation, thereby leading to a loss of tight junctions. These studies define how an extracellular cue signals to the polarity machinery to control epithelial cell morphology.</description><subject>Analysis</subject><subject>Biological and medical sciences</subject><subject>Cancer</subject><subject>Care and treatment</subject><subject>Cell lines</subject><subject>Cell physiology</subject><subject>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</subject><subject>Epithelial cells</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene expression regulation</subject><subject>Immunoblotting</subject><subject>Immunoprecipitation</subject><subject>Molecular and cellular biology</subject><subject>Observations</subject><subject>Phenotypes</subject><subject>Phosphorylation</subject><subject>Proteins</subject><subject>Receptors</subject><subject>Small interfering RNA</subject><subject>Tight junctions</subject><issn>0036-8075</issn><issn>1095-9203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><recordid>eNqN0c9rHCEUB3ApDXSb5txLD15a6GHSp86oc0yXZBNYmiU_euzgODo1uONGXej-W_1D-jdV2BAI5LB4EH2f70OeCH0kcEoI5d-SdmbSphygEUS-QTMCbVO1FNhbNANgvJIgmnfofUoPAKXWshn6dWPGrVfZhQkHi_Nvg1fBq-jyDq9iyMZNeKUix_0O3y0u_v3FN0abTQ4x4XmYcgw-4fONK0HvlMdz4z1eeZWy06XHB3RklU_m5Gk_RvcX53fzy2p5vbiany2rsW4gV73Wtpdy4Bxoy2gviGhBy4HKRjbQWrADpbWsbT1IxYToG9C04aA0o0QIxY7Rl33fTQyPW5Nyt3ZJl7eoyYRt6goSTIq2wGoPR-VN5yYbclR6NJOJyofJWFeuzwgjAAIEL_70FV_WYNZOvxr4-iJQTDZ_8qi2KXVXtz8Ot9c_D7ffFwdbuVi-tJ-fJqeSVt5GNWmXuk10axV3HeGcyIaL4j7t3UMqn_9cZ7IusyXsP1JDxCg</recordid><startdate>20050311</startdate><enddate>20050311</enddate><creator>Ozdamar, Barish</creator><creator>Bose, Rohit</creator><creator>Barrios-Rodiles, Miriam</creator><creator>Wang, Hong-Rui</creator><creator>Zhang, Yue</creator><creator>Wrana, Jeffrey L.</creator><general>American Association for the Advancement of Science</general><scope>IQODW</scope><scope>8GL</scope><scope>IBG</scope><scope>IOV</scope><scope>ISN</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>20050311</creationdate><title>Regulation of the Polarity Protein Par6 by TGFβ Receptors Controls Epithelial Cell Plasticity</title><author>Ozdamar, Barish ; Bose, Rohit ; Barrios-Rodiles, Miriam ; Wang, Hong-Rui ; Zhang, Yue ; Wrana, Jeffrey L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-g450t-bccfb88d6602932b71790c8d2858509f0fd22484f4d8a377b50c2560ac32177a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Analysis</topic><topic>Biological and medical sciences</topic><topic>Cancer</topic><topic>Care and treatment</topic><topic>Cell lines</topic><topic>Cell physiology</topic><topic>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</topic><topic>Epithelial cells</topic><topic>Fundamental and applied biological sciences. 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| ispartof | Science (American Association for the Advancement of Science), 2005-03, Vol.307 (5715), p.1603-1609 |
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| source | American Association for the Advancement of Science; JSTOR |
| subjects | Analysis Biological and medical sciences Cancer Care and treatment Cell lines Cell physiology Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes Epithelial cells Fundamental and applied biological sciences. Psychology Gene expression regulation Immunoblotting Immunoprecipitation Molecular and cellular biology Observations Phenotypes Phosphorylation Proteins Receptors Small interfering RNA Tight junctions |
| title | Regulation of the Polarity Protein Par6 by TGFβ Receptors Controls Epithelial Cell Plasticity |
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