{"corpus_id":23778597,"paper_sha":"361cd11eccd1ca33bfa83dd0a4625631d40eb9c3","doi":"10.1074/jbc.M207014200","arxiv_id":null,"pmid":12446733,"pmcid":null,"mag_id":2059300671,"dblp_id":null,"acl_id":null,"title":"The Requirement of Specific Membrane Domains for Raf-1 Phosphorylation and Activation*","year":2003,"publication_date":"2003-01-31","venue":"Journal of Biological Chemistry","journal":{"name":"The Journal of Biological Chemistry","pages":"3185 - 3196","volume":"278"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle"],"pubmed_pub_types":["Journal Article","Research Support, U.S. Gov't, P.H.S."],"s2_fields_of_study":["Biology","Medicine","Chemistry"],"reference_count":74,"citation_count":55,"influential_citation_count":3,"is_open_access":false,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"Amino Acid Sequence","mj":false,"ui":"D000595"},{"d":"Animals","mj":false,"ui":"D000818"},{"d":"Binding Sites","mj":false,"ui":"D001665"},{"d":"COS Cells","mj":false,"ui":"D019556"},{"d":"Chlorocebus aethiops","mj":false,"ui":"D002522"},{"d":"DNA, Complementary","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"}],"ui":"D018076"},{"d":"Genes, ras","mj":false,"ui":"D011905"},{"d":"Membrane Microdomains","mj":false,"qs":[{"q":"chemistry","mj":false,"ui":"Q000737"},{"q":"metabolism","mj":true,"ui":"Q000378"}],"ui":"D021962"},{"d":"Molecular Sequence Data","mj":false,"ui":"D008969"},{"d":"Phosphorylation","mj":false,"ui":"D010766"},{"d":"Phosphoserine","mj":false,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D010768"},{"d":"Phosphotyrosine","mj":false,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D019000"},{"d":"Proto-Oncogene Proteins c-raf","mj":false,"qs":[{"q":"chemistry","mj":true,"ui":"Q000737"},{"q":"genetics","mj":false,"ui":"Q000235"},{"q":"metabolism","mj":true,"ui":"Q000378"}],"ui":"D019908"},{"d":"Recombinant Proteins","mj":false,"qs":[{"q":"chemistry","mj":false,"ui":"Q000737"},{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D011994"},{"d":"Restriction Mapping","mj":false,"ui":"D015183"},{"d":"Transfection","mj":false,"ui":"D014162"}],"chemicals":[{"n":"DNA, Complementary","ui":"D018076","reg":"0"},{"n":"Recombinant Proteins","ui":"D011994","reg":"0"},{"n":"Phosphoserine","ui":"D010768","reg":"17885-08-4"},{"n":"Phosphotyrosine","ui":"D019000","reg":"21820-51-9"},{"n":"Proto-Oncogene Proteins c-raf","ui":"D019908","reg":"EC 2.7.11.1"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":null,"s2_open_access_landing_url":null,"s2_open_access_license":null,"s2_open_access_status":null,"pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"Activation of Raf-1 by Ras requires recruitment to the membrane as well as additional phosphorylations, including phosphorylation at serine 338 (Ser-338) and tyrosine 341 (Tyr-341). In this study we show that Tyr-341 participates in the recruitment of Raf-1 to specialized membrane domains called “rafts,” which are required for Raf-1 to be phosphorylated on Ser-338. Raf-1 is also thought to be recruited to the small G protein Rap1 upon GTP loading of Rap1. However, this does not result in Raf-1 activation. We propose that this is because Raf-1 is not phosphorylated on Tyr-341 upon recruitment to Rap1. Redirecting Rap1 to Ras-containing membranes or mimicking Tyr-341 phosphorylation of Raf-1 by mutation converts Rap1 into an activator of Raf-1. In contrast to Raf-1, B-Raf is activated by Rap1. We suggest that this is because B-Raf activation is independent of tyrosine phosphorylation. Moreover, mutants that render B-Raf dependent on tyrosine phosphorylation are no longer activated by Rap1.","claims":[{"public_id":"cl_099028ae12ee3c1e4ae4c74538dc1b92","status":"active","text":"B-Raf activation by Rap1 is independent of tyrosine phosphorylation, and making B-Raf dependent on tyrosine phosphorylation abolishes Rap1-mediated activation.","confidence":0.97,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_099028ae12ee3c1e4ae4c74538dc1b92"},{"public_id":"cl_4deb1991605151d5762c8ed2741f3fcb","status":"active","text":"Recruitment of Raf-1 to Rap1 does not activate Raf-1 because Raf-1 is not phosphorylated on tyrosine 341 in that context.","confidence":0.95,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous 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