Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive
The target of rapamycin (TOR) is a highly conserved protein kinase and a central controller of cell growth. In budding yeast, TOR is found in structurally and functionally distinct protein complexes: TORC1 and TORC2. A mammalian counterpart of TORC1 (mTORC1) has been described, but it is not known w...
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| Veröffentlicht in: | Nature cell biology 2004-11, Vol.6 (11), p.1122-1128 |
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| creator | Jacinto, Estela Loewith, Robbie Schmidt, Anja Lin, Shuo Rüegg, Markus A. Hall, Alan Hall, Michael N. |
| description | The target of rapamycin (TOR) is a highly conserved protein kinase and a central controller of cell growth. In budding yeast, TOR is found in structurally and functionally distinct protein complexes: TORC1 and TORC2. A mammalian counterpart of TORC1 (mTORC1) has been described, but it is not known whether TORC2 is conserved in mammals. Here, we report that a mammalian counterpart of TORC2 (mTORC2) also exists. mTORC2 contains mTOR, mLST8 and mAVO3, but not raptor. Like yeast TORC2, mTORC2 is rapamycin insensitive and seems to function upstream of Rho GTPases to regulate the actin cytoskeleton. mTORC2 is not upstream of the mTORC1 effector S6K. Thus, two distinct TOR complexes constitute a primordial signalling network conserved in eukaryotic evolution to control the fundamental process of cell growth. |
| doi_str_mv | 10.1038/ncb1183 |
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In budding yeast, TOR is found in structurally and functionally distinct protein complexes: TORC1 and TORC2. A mammalian counterpart of TORC1 (mTORC1) has been described, but it is not known whether TORC2 is conserved in mammals. Here, we report that a mammalian counterpart of TORC2 (mTORC2) also exists. mTORC2 contains mTOR, mLST8 and mAVO3, but not raptor. Like yeast TORC2, mTORC2 is rapamycin insensitive and seems to function upstream of Rho GTPases to regulate the actin cytoskeleton. mTORC2 is not upstream of the mTORC1 effector S6K. Thus, two distinct TOR complexes constitute a primordial signalling network conserved in eukaryotic evolution to control the fundamental process of cell growth.</description><identifier>ISSN: 1465-7392</identifier><identifier>EISSN: 1476-4679</identifier><identifier>DOI: 10.1038/ncb1183</identifier><identifier>PMID: 15467718</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Actin ; Actins - physiology ; Amino acids ; Animals ; Biomedical and Life Sciences ; Brewer's yeast ; Cancer Research ; Cell Biology ; Cell Cycle Proteins ; Cell growth ; Cell Line ; Cytoskeleton ; Cytoskeleton - physiology ; Developmental Biology ; Genetic aspects ; Genomes ; Health aspects ; Humans ; Insects ; Kinases ; letter ; Life Sciences ; Mammals ; Mice ; NIH 3T3 Cells ; Phosphatidylinositol 3-Kinases ; Phosphotransferases (Alcohol Group Acceptor) - physiology ; Physiological aspects ; Proteins ; Rapamycin ; Sirolimus - pharmacology ; Stem Cells ; Upstream ; Yeast ; Yeasts</subject><ispartof>Nature cell biology, 2004-11, Vol.6 (11), p.1122-1128</ispartof><rights>Springer Nature Limited 2004</rights><rights>COPYRIGHT 2004 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Nov 2004</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c504t-11f4900990f037a1fe923736769866e74e8e2d3e7f328ea435a7ddbd5f6288b03</citedby><cites>FETCH-LOGICAL-c504t-11f4900990f037a1fe923736769866e74e8e2d3e7f328ea435a7ddbd5f6288b03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/ncb1183$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/ncb1183$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15467718$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jacinto, Estela</creatorcontrib><creatorcontrib>Loewith, Robbie</creatorcontrib><creatorcontrib>Schmidt, Anja</creatorcontrib><creatorcontrib>Lin, Shuo</creatorcontrib><creatorcontrib>Rüegg, Markus A.</creatorcontrib><creatorcontrib>Hall, Alan</creatorcontrib><creatorcontrib>Hall, Michael N.</creatorcontrib><title>Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive</title><title>Nature cell biology</title><addtitle>Nat Cell Biol</addtitle><addtitle>Nat Cell Biol</addtitle><description>The target of rapamycin (TOR) is a highly conserved protein kinase and a central controller of cell growth. In budding yeast, TOR is found in structurally and functionally distinct protein complexes: TORC1 and TORC2. A mammalian counterpart of TORC1 (mTORC1) has been described, but it is not known whether TORC2 is conserved in mammals. Here, we report that a mammalian counterpart of TORC2 (mTORC2) also exists. mTORC2 contains mTOR, mLST8 and mAVO3, but not raptor. Like yeast TORC2, mTORC2 is rapamycin insensitive and seems to function upstream of Rho GTPases to regulate the actin cytoskeleton. mTORC2 is not upstream of the mTORC1 effector S6K. Thus, two distinct TOR complexes constitute a primordial signalling network conserved in eukaryotic evolution to control the fundamental process of cell growth.</description><subject>Actin</subject><subject>Actins - physiology</subject><subject>Amino acids</subject><subject>Animals</subject><subject>Biomedical and Life Sciences</subject><subject>Brewer's yeast</subject><subject>Cancer Research</subject><subject>Cell Biology</subject><subject>Cell Cycle Proteins</subject><subject>Cell growth</subject><subject>Cell Line</subject><subject>Cytoskeleton</subject><subject>Cytoskeleton - physiology</subject><subject>Developmental Biology</subject><subject>Genetic aspects</subject><subject>Genomes</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Insects</subject><subject>Kinases</subject><subject>letter</subject><subject>Life Sciences</subject><subject>Mammals</subject><subject>Mice</subject><subject>NIH 3T3 Cells</subject><subject>Phosphatidylinositol 3-Kinases</subject><subject>Phosphotransferases (Alcohol Group Acceptor) - physiology</subject><subject>Physiological aspects</subject><subject>Proteins</subject><subject>Rapamycin</subject><subject>Sirolimus - pharmacology</subject><subject>Stem Cells</subject><subject>Upstream</subject><subject>Yeast</subject><subject>Yeasts</subject><issn>1465-7392</issn><issn>1476-4679</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNptkV1rFDEUhoMotlbxH0hQ8ONiar4mmVyW0mqhUqjrdchmTtbUmcw2yUj335tlF8oWyUUOOc95T857EHpLySklvPsa3ZLSjj9Dx1Qo2Qip9PNtLNtGcc2O0Kuc7wihQhD1Eh3RthKKdsdo8cOOox2CjXhxc4vdNK4HeMCsRrGkaci4_AZsXQkRu02Z8h8YoEwR29jjkHGyaztuXM2GmCHmUMJfeI1eeDtkeLO_T9Cvy4vF-ffm-ubb1fnZdeNaIkpDqReaEK2JJ1xZ6kEzrrhUUndSghLQAes5KM9ZB1bw1qq-X_atl6zrloSfoI873XWa7mfIxYwhOxgGG2Gas5GKMC6ZrOD7J-DdNKdY_2YYY1xITboKfdhBKzuACdFPJVm3VTRn1dvakmpdqdP_UPX0MIZqGvhQ3w8KvhwUbI2Fh7Kyc87m6uftIftpx7o05ZzAm3UKo00bQ4nZLtrsF13Jd_uJ5uUI_SO332wFPu-AXFNxBelx5Kda_wAhIqz3</recordid><startdate>20041101</startdate><enddate>20041101</enddate><creator>Jacinto, Estela</creator><creator>Loewith, Robbie</creator><creator>Schmidt, Anja</creator><creator>Lin, Shuo</creator><creator>Rüegg, Markus A.</creator><creator>Hall, Alan</creator><creator>Hall, Michael N.</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>ISR</scope><scope>3V.</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20041101</creationdate><title>Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive</title><author>Jacinto, Estela ; Loewith, Robbie ; Schmidt, Anja ; Lin, Shuo ; Rüegg, Markus A. ; Hall, Alan ; Hall, Michael N.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c504t-11f4900990f037a1fe923736769866e74e8e2d3e7f328ea435a7ddbd5f6288b03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Actin</topic><topic>Actins - 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Academic</collection><jtitle>Nature cell biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jacinto, Estela</au><au>Loewith, Robbie</au><au>Schmidt, Anja</au><au>Lin, Shuo</au><au>Rüegg, Markus A.</au><au>Hall, Alan</au><au>Hall, Michael N.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive</atitle><jtitle>Nature cell biology</jtitle><stitle>Nat Cell Biol</stitle><addtitle>Nat Cell Biol</addtitle><date>2004-11-01</date><risdate>2004</risdate><volume>6</volume><issue>11</issue><spage>1122</spage><epage>1128</epage><pages>1122-1128</pages><issn>1465-7392</issn><eissn>1476-4679</eissn><abstract>The target of rapamycin (TOR) is a highly conserved protein kinase and a central controller of cell growth. In budding yeast, TOR is found in structurally and functionally distinct protein complexes: TORC1 and TORC2. A mammalian counterpart of TORC1 (mTORC1) has been described, but it is not known whether TORC2 is conserved in mammals. Here, we report that a mammalian counterpart of TORC2 (mTORC2) also exists. mTORC2 contains mTOR, mLST8 and mAVO3, but not raptor. Like yeast TORC2, mTORC2 is rapamycin insensitive and seems to function upstream of Rho GTPases to regulate the actin cytoskeleton. mTORC2 is not upstream of the mTORC1 effector S6K. Thus, two distinct TOR complexes constitute a primordial signalling network conserved in eukaryotic evolution to control the fundamental process of cell growth.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>15467718</pmid><doi>10.1038/ncb1183</doi><tpages>7</tpages></addata></record> |
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| subjects | Actin Actins - physiology Amino acids Animals Biomedical and Life Sciences Brewer's yeast Cancer Research Cell Biology Cell Cycle Proteins Cell growth Cell Line Cytoskeleton Cytoskeleton - physiology Developmental Biology Genetic aspects Genomes Health aspects Humans Insects Kinases letter Life Sciences Mammals Mice NIH 3T3 Cells Phosphatidylinositol 3-Kinases Phosphotransferases (Alcohol Group Acceptor) - physiology Physiological aspects Proteins Rapamycin Sirolimus - pharmacology Stem Cells Upstream Yeast Yeasts |
| title | Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive |
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