{"id":183,"date":"2012-01-14T23:05:00","date_gmt":"2012-01-14T23:05:00","guid":{"rendered":"http:\/\/lucasgferreira.wordpress.com\/2012\/01\/14\/camp-inhibits-mammalian-target-of-rapamycin-complex-1-and-2-mtorc1-and-2-by-promoting-complex-dissociation-and-inhibiting-mtor-kinase-activity"},"modified":"2012-01-14T23:05:00","modified_gmt":"2012-01-14T23:05:00","slug":"camp-inhibits-mammalian-target-of-rapamycin-complex-1-and-2-mtorc1-and-2-by-promoting-complex-dissociation-and-inhibiting-mtor-kinase-activity","status":"publish","type":"post","link":"https:\/\/blog.ufes.br\/lucasgf\/?p=183","title":{"rendered":"cAMP inhibits mammalian target of rapamycin complex-1 and -2 (mTORC1 and 2) by promoting complex dissociation and inhibiting mTOR kinase activity."},"content":{"rendered":"

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O estudo de Xie et al (2012) publicado essa semana no <\/i>Cellular Signalling apresenta novos dados que auxiliam na compreens\u00e3o acerca da regula\u00e7\u00e3o do complexo mTORC1, evidenciando uma a\u00e7\u00e3o inibit\u00f3ria do segundo AMPc sobre este complexo.<\/i><\/div>\n

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Cell Signal.<\/a> 2011 Dec;23(12):1927-35. Epub 2011 Jul 6.<\/span><\/div>\n

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Xie J<\/a>, Ponuwei GA<\/a>, Moore CE<\/a>, Willars GB<\/a>, Tee AR<\/a>, Herbert TP<\/a>.<\/div>\n
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Source<\/h3>\n
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Department of Cell Physiology and Pharmacology, University of Leicester, The Henry Wellcome Building, University Road, Leicester LE1 9HN, UK<\/span>.<\/span><\/div>\n<\/div>\n
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Abstract<\/h3>\n
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cAMP and mTOR signalling pathways control a number of critical cellular processes including metabolism, protein synthesis, proliferation and cell survival and therefore understanding the signalling events which integrate these two signalling pathways is of particular interest. In this study, we show that the pharmacological elevation of [cAMP](i) in mouse embryonic fibroblasts (MEFs) and human embryonic kidney 293 (HEK293) cells inhibits mTORC1 activation via a PKA-dependent mechanism. Although the inhibitory effect of cAMP on mTOR could be mediated by impinging on signalling cascades (i.e. PKB, MAPK and AMPK) that inhibit TSC1\/2, an upstream negative regulator of mTORC1, we show that cAMP inhibits mTORC1 in TSC2 knockout (TSC2(-\/-)) MEFs. We also show that cAMP inhibits insulin and amino acid-stimulated mTORC1 activation independently of Rheb, Rag GTPases, TSC2, PKB, MAPK and AMPK, indicating that cAMP may act independently of known regulatory inputs into mTOR. Moreover, we show that the prolonged elevation in [cAMP](i) can also inhibit mTORC2. We provide evidence that this cAMP-dependent inhibition of mTORC1\/2 is caused by the dissociation of mTORC1 and 2 and a reduction in mTOR catalytic activity, as determined by its auto-phosphorylation on Ser2481. Taken together, these results provide an important insight into how cAMP signals to mTOR and down-regulates its activity, which may lead to the identification of novel drug targets to inhibit mTOR that could be used for the treatment and prevention of human diseases such as cancer.<\/div>\n
Copyright \u00a9 2011 Elsevier Inc. All rights reserved.<\/div>\n<\/div>\n
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PMID:<\/dt>\n

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21763421<\/dd>\n

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[PubMed – indexed for MEDLINE] <\/dd>\n
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PMCID: PMC3189512<\/dt>\n
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Artigo completo: http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3189512\/<\/a><\/p>\n

<\/div>\n","protected":false},"excerpt":{"rendered":"

O estudo de Xie et al (2012) publicado essa semana no Cellular Signalling apresenta novos dados que auxiliam na compreens\u00e3o acerca da regula\u00e7\u00e3o do complexo mTORC1, evidenciando uma a\u00e7\u00e3o inibit\u00f3ria do segundo AMPc sobre este complexo. Cell Signal. 2011 Dec;23(12):1927-35. Epub … Continue lendo →<\/span><\/a><\/p>\n","protected":false},"author":9,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_bbp_topic_count":0,"_bbp_reply_count":0,"_bbp_total_topic_count":0,"_bbp_total_reply_count":0,"_bbp_voice_count":0,"_bbp_anonymous_reply_count":0,"_bbp_topic_count_hidden":0,"_bbp_reply_count_hidden":0,"_bbp_forum_subforum_count":0,"_uag_custom_page_level_css":"","footnotes":""},"categories":[21,34,36,39],"tags":[],"class_list":["post-183","post","type-post","status-publish","format-standard","hentry","category-fisiologia","category-paper","category-plasticidade-muscular","category-sinalizacao-celular"],"uagb_featured_image_src":{"full":false,"thumbnail":false,"medium":false,"medium_large":false,"large":false,"1536x1536":false,"2048x2048":false,"post-thumbnail":false},"uagb_author_info":{"display_name":"Lucas Guimar\u00e3es Ferreira","author_link":"https:\/\/blog.ufes.br\/lucasgf\/?author=9"},"uagb_comment_info":4,"uagb_excerpt":"O estudo de Xie et al (2012) publicado essa semana no Cellular Signalling apresenta novos dados que auxiliam na compreens\u00e3o acerca da regula\u00e7\u00e3o do complexo mTORC1, evidenciando uma a\u00e7\u00e3o inibit\u00f3ria do segundo AMPc sobre este complexo. Cell Signal. 2011 Dec;23(12):1927-35. Epub … Continue lendo →","_links":{"self":[{"href":"https:\/\/blog.ufes.br\/lucasgf\/index.php?rest_route=\/wp\/v2\/posts\/183","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/blog.ufes.br\/lucasgf\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/blog.ufes.br\/lucasgf\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/blog.ufes.br\/lucasgf\/index.php?rest_route=\/wp\/v2\/users\/9"}],"replies":[{"embeddable":true,"href":"https:\/\/blog.ufes.br\/lucasgf\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=183"}],"version-history":[{"count":0,"href":"https:\/\/blog.ufes.br\/lucasgf\/index.php?rest_route=\/wp\/v2\/posts\/183\/revisions"}],"wp:attachment":[{"href":"https:\/\/blog.ufes.br\/lucasgf\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=183"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blog.ufes.br\/lucasgf\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=183"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blog.ufes.br\/lucasgf\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=183"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}