{"id":"https://openalex.org/W1990872004","doi":"https://doi.org/10.1097/01.mco.0000134364.61406.26","title":"Signaling pathways weigh in on decisions to make or break skeletal muscle","display_name":"Signaling pathways weigh in on decisions to make or break skeletal muscle","publication_year":2004,"publication_date":"2004-06-10","ids":{"openalex":"https://openalex.org/W1990872004","doi":"https://doi.org/10.1097/01.mco.0000134364.61406.26","mag":"1990872004","pmid":"https://pubmed.ncbi.nlm.nih.gov/15192448"},"language":"en","primary_location":{"id":"doi:10.1097/01.mco.0000134364.61406.26","doi":"https://doi.org/10.1097/01.mco.0000134364.61406.26","is_oa":false,"landing_page_url":"https://doi.org/10.1097/01.mco.0000134364.61406.26","pdf_url":null,"source":{"id":"https://openalex.org/S75106429","display_name":"Current Opinion in Clinical Nutrition & Metabolic Care","issn_l":"1363-1950","issn":["1363-1950","1473-6519"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","doyens","jufo-1","ki-jl-1","medline","norway-1","poland-100","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310315671","host_organization_name":"Lippincott Williams & Wilkins","host_organization_lineage":["https://openalex.org/P4310315671","https://openalex.org/P4310318547"],"host_organization_lineage_names":["Lippincott Williams & Wilkins","Wolters Kluwer"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Current Opinion in Clinical Nutrition and Metabolic Care","raw_type":"journal-article"},"volume":null,"type":"review","is_traditional":true,"indexed_in":["crossref","pubmed"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5088452270","display_name":"Denis C. Guttridge","orcid":"https://orcid.org/0000-0002-7276-6609","observed_orcids":["https://orcid.org/0000-0002-7276-6609"]},"institutions":[{"id":"https://openalex.org/I4210132946","display_name":"Tuberous Sclerosis Association","ror":"https://ror.org/0306fdh09","country_code":"GB","type":"nonprofit","lineage":["https://openalex.org/I4210132946"]},{"id":"https://openalex.org/I52357470","display_name":"The Ohio State University","ror":"https://ror.org/00rs6vg23","country_code":"US","type":"education","lineage":["https://openalex.org/I52357470"]}],"countries":["GB","US"],"is_corresponding":true,"raw_author_name":"Denis C Guttridge","raw_affiliation_strings":["Division of Human Cancer Genetics, The Ohio State University, Columbus, Ohio, USA. guttridge-1@medctr.osu.edu","Division of Human Cancer Genetics, The Ohio State University, Columbus, Ohio, USA","TGF: transforming growth factor","TNF: tumor necrosis factor","Tsc: tuberous sclerosis complex","e-mail: [email\u00a0protected]","fax: +1 614 688 4006","mTOR: mammalian target of rapamycin","to Denis Guttridge, Division of Human Cancer Genetics, The Ohio State University, 560 MRF, 420 W. 12th Ave., Columbus, OH 43210, USA Tel: +1 614 688 3137"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Human Cancer Genetics, The Ohio State University, Columbus, Ohio, USA. guttridge-1@medctr.osu.edu","institution_ids":["https://openalex.org/I52357470"]},{"raw_affiliation_string":"Division of Human Cancer Genetics, The Ohio State University, Columbus, Ohio, USA","institution_ids":["https://openalex.org/I52357470"]},{"raw_affiliation_string":"TGF: transforming growth factor","institution_ids":[]},{"raw_affiliation_string":"TNF: tumor necrosis factor","institution_ids":[]},{"raw_affiliation_string":"Tsc: tuberous sclerosis complex","institution_ids":["https://openalex.org/I4210132946"]},{"raw_affiliation_string":"e-mail: [email\u00a0protected]","institution_ids":[]},{"raw_affiliation_string":"fax: +1 614 688 4006","institution_ids":[]},{"raw_affiliation_string":"mTOR: mammalian target of rapamycin","institution_ids":[]},{"raw_affiliation_string":"to Denis Guttridge, Division of Human Cancer Genetics, The Ohio State University, 560 MRF, 420 W. 12th Ave., Columbus, OH 43210, USA Tel: +1 614 688 3137","institution_ids":["https://openalex.org/I52357470"]}]}],"institutions":[],"countries_distinct_count":2,"institutions_distinct_count":2,"corresponding_author_ids":["https://openalex.org/A5088452270"],"corresponding_institution_ids":["https://openalex.org/I4210132946","https://openalex.org/I52357470"],"apc_list":null,"apc_paid":null,"fwci":1.1228,"has_fulltext":false,"cited_by_count":148,"citation_normalized_percentile":{"value":0.72858644,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":88,"max":99},"biblio":{"volume":"7","issue":"4","first_page":"443","last_page":"450"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10441","display_name":"Muscle Physiology and Disorders","score":0.9984999895095825,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T10441","display_name":"Muscle Physiology and Disorders","score":0.9984999895095825,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T11399","display_name":"Muscle metabolism and nutrition","score":0.0010999999940395355,"subfield":{"id":"https://openalex.org/subfields/2916","display_name":"Nutrition and Dietetics"},"field":{"id":"https://openalex.org/fields/29","display_name":"Nursing"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10397","display_name":"Nutrition and Health in Aging","score":0.0,"subfield":{"id":"https://openalex.org/subfields/2737","display_name":"Physiology (medical)"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/muscle-hypertrophy","display_name":"muscle hypertrophy","score":0.8690000176429749},{"id":"https://openalex.org/keywords/muscle-atrophy","display_name":"muscle atrophy","score":0.8980000019073486},{"id":"https://openalex.org/keywords/pi3k-akt-signaling","display_name":"PI3K/Akt signaling","score":0.9430000185966492},{"id":"https://openalex.org/keywords/myostatin","display_name":"myostatin","score":0.921999990940094},{"id":"https://openalex.org/keywords/nf-kappab","display_name":"NF-\u03baB","score":0.953000009059906},{"id":"https://openalex.org/keywords/insulin-like-growth-factor-i","display_name":"insulin-like growth factor I","score":0.8230000138282776},{"id":"https://openalex.org/keywords/mtor","display_name":"mTOR","score":0.9509999752044678},{"id":"https://openalex.org/keywords/p70s6k","display_name":"p70S6K","score":0.9959999918937683},{"id":"https://openalex.org/keywords/tsc2","display_name":"TSC2","score":0.9710000157356262},{"id":"https://openalex.org/keywords/myod","display_name":"MyoD","score":0.9890000224113464},{"id":"https://openalex.org/keywords/myogenesis","display_name":"myogenesis","score":0.9179999828338623},{"id":"https://openalex.org/keywords/protein-synthesis","display_name":"protein synthesis","score":0.6110000014305115}],"concepts":[{"id":"https://openalex.org/C2777488582","wikidata":"https://www.wikidata.org/wiki/Q29630","display_name":"Myostatin","level":3,"score":0.9731000661849976},{"id":"https://openalex.org/C2778106681","wikidata":"https://www.wikidata.org/wiki/Q416095","display_name":"MyoD","level":4,"score":0.916398286819458},{"id":"https://openalex.org/C3763915","wikidata":"https://www.wikidata.org/wiki/Q3331437","display_name":"Myogenesis","level":3,"score":0.8942723870277405},{"id":"https://openalex.org/C75217442","wikidata":"https://www.wikidata.org/wiki/Q423650","display_name":"Protein kinase B","level":3,"score":0.7477364540100098},{"id":"https://openalex.org/C86554907","wikidata":"https://www.wikidata.org/wiki/Q285613","display_name":"PI3K/AKT/mTOR pathway","level":3,"score":0.6383631229400635},{"id":"https://openalex.org/C62478195","wikidata":"https://www.wikidata.org/wiki/Q828130","display_name":"Signal transduction","level":2,"score":0.5627956390380859},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.5624004006385803},{"id":"https://openalex.org/C2779959927","wikidata":"https://www.wikidata.org/wiki/Q1048687","display_name":"Skeletal muscle","level":2,"score":0.5087507367134094},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.5009472370147705},{"id":"https://openalex.org/C2909166674","wikidata":"https://www.wikidata.org/wiki/Q416095","display_name":"MyoD Protein","level":5,"score":0.4919869601726532},{"id":"https://openalex.org/C207200792","wikidata":"https://www.wikidata.org/wiki/Q428914","display_name":"Myocyte","level":2,"score":0.4532899856567383},{"id":"https://openalex.org/C167414201","wikidata":"https://www.wikidata.org/wiki/Q1955391","display_name":"Muscle hypertrophy","level":2,"score":0.4430704116821289},{"id":"https://openalex.org/C86339819","wikidata":"https://www.wikidata.org/wiki/Q407384","display_name":"Transcription factor","level":3,"score":0.4377284348011017},{"id":"https://openalex.org/C134018914","wikidata":"https://www.wikidata.org/wiki/Q162606","display_name":"Endocrinology","level":1,"score":0.23013195395469666},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.08831807971000671},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.0}],"mesh":[{"descriptor_ui":"D000818","descriptor_name":"Animals","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D009133","descriptor_name":"Muscular Atrophy","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D011494","descriptor_name":"Protein Kinases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D011518","descriptor_name":"Proto-Oncogene Proteins","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D013002","descriptor_name":"Somatomedins","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D015398","descriptor_name":"Signal Transduction","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D016212","descriptor_name":"Transforming Growth Factor beta","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D016328","descriptor_name":"NF-kappa B","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D017346","descriptor_name":"Protein Serine-Threonine Kinases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D018482","descriptor_name":"Muscle, Skeletal","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D018482","descriptor_name":"Muscle, Skeletal","qualifier_ui":"Q000502","qualifier_name":"physiology","is_major_topic":true},{"descriptor_ui":"D051057","descriptor_name":"Proto-Oncogene Proteins c-akt","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D055435","descriptor_name":"Myostatin","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D058570","descriptor_name":"TOR Serine-Threonine Kinases","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":2,"locations":[{"id":"doi:10.1097/01.mco.0000134364.61406.26","doi":"https://doi.org/10.1097/01.mco.0000134364.61406.26","is_oa":false,"landing_page_url":"https://doi.org/10.1097/01.mco.0000134364.61406.26","pdf_url":null,"source":{"id":"https://openalex.org/S75106429","display_name":"Current Opinion in Clinical Nutrition & Metabolic Care","issn_l":"1363-1950","issn":["1363-1950","1473-6519"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","doyens","jufo-1","ki-jl-1","medline","norway-1","poland-100","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310315671","host_organization_name":"Lippincott Williams & Wilkins","host_organization_lineage":["https://openalex.org/P4310315671","https://openalex.org/P4310318547"],"host_organization_lineage_names":["Lippincott Williams & Wilkins","Wolters Kluwer"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Current Opinion in Clinical Nutrition and Metabolic Care","raw_type":"journal-article"},{"id":"pmid:15192448","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/15192448","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Current opinion in clinical nutrition and metabolic care","raw_type":"Journal Article"}],"best_oa_location":null,"sustainable_development_goals":[{"score":0.9391000270843506,"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":70,"referenced_works":["https://openalex.org/W137188978","https://openalex.org/W1530473805","https://openalex.org/W1586159393","https://openalex.org/W1865608113","https://openalex.org/W1910033896","https://openalex.org/W1930882462","https://openalex.org/W1952579501","https://openalex.org/W1965044262","https://openalex.org/W1967544564","https://openalex.org/W1970674526","https://openalex.org/W1973487146","https://openalex.org/W1978278774","https://openalex.org/W1978625554","https://openalex.org/W1982422465","https://openalex.org/W1985266648","https://openalex.org/W1988711802","https://openalex.org/W1990007701","https://openalex.org/W1990205368","https://openalex.org/W2004966843","https://openalex.org/W2009324447","https://openalex.org/W2011282245","https://openalex.org/W2025463260","https://openalex.org/W2025796648","https://openalex.org/W2026192447","https://openalex.org/W2034074403","https://openalex.org/W2035857855","https://openalex.org/W2042087846","https://openalex.org/W2048134135","https://openalex.org/W2053079324","https://openalex.org/W2053648381","https://openalex.org/W2054027756","https://openalex.org/W2054368198","https://openalex.org/W2063334442","https://openalex.org/W2064895186","https://openalex.org/W2064931913","https://openalex.org/W2066121149","https://openalex.org/W2067938485","https://openalex.org/W2076277955","https://openalex.org/W2076954734","https://openalex.org/W2079300172","https://openalex.org/W2082784172","https://openalex.org/W2083700023","https://openalex.org/W2084314951","https://openalex.org/W2089333275","https://openalex.org/W2092846222","https://openalex.org/W2103031848","https://openalex.org/W2116082328","https://openalex.org/W2118986158","https://openalex.org/W2122043314","https://openalex.org/W2128303661","https://openalex.org/W2130122556","https://openalex.org/W2133055307","https://openalex.org/W2138089538","https://openalex.org/W2140622735","https://openalex.org/W2145274091","https://openalex.org/W2146431980","https://openalex.org/W2146857824","https://openalex.org/W2147921405","https://openalex.org/W2149993139","https://openalex.org/W2150684620","https://openalex.org/W2152128819","https://openalex.org/W2153289066","https://openalex.org/W2155253974","https://openalex.org/W2157891228","https://openalex.org/W2158254766","https://openalex.org/W2165868509","https://openalex.org/W2166781237","https://openalex.org/W2183086158","https://openalex.org/W3123206457","https://openalex.org/W4300790656"],"related_works":["https://openalex.org/W30273463","https://openalex.org/W2116769367","https://openalex.org/W1993476327","https://openalex.org/W7096181829","https://openalex.org/W1990911170","https://openalex.org/W7099469742","https://openalex.org/W1996657560","https://openalex.org/W2109017400","https://openalex.org/W2150059080","https://openalex.org/W2066056709"],"abstract_inverted_index":{"PURPOSE":[0],"OF":[1],"REVIEW:":[2],"Regulation":[3],"of":[4,14,34,50,60,67,131,145,170,177],"muscle":[5,68,91,123,183,221,243],"size":[6],"is":[7,19,150],"essential":[8],"for":[9,194],"proper":[10],"development":[11],"and":[12,39,79,104,143,203,216,232],"homeostasis":[13],"adult":[15],"musculature.":[16],"This":[17],"regulation":[18,66,191],"mediated":[20],"in":[21,64,90,113,122,238],"large":[22],"part":[23,197],"by":[24,106,118,139,153,172,188,212],"signal":[25],"transduction":[26],"pathways":[27,44,219],"that":[28,45],"promote":[29],"the":[30,48,58,61,65,87,141,157,186,195,210],"synthesis":[31,84,142],"or":[32,229],"breakdown":[33],"skeletal":[35],"muscle.":[36],"PI(3)K/Akt,":[37],"myostatin":[38,120,148,158,231],"NF-kappaB":[40,161,178,217,233],"represent":[41],"three":[42],"such":[43],"will":[46],"be":[47],"focus":[49],"this":[51,190],"review.":[52],"RECENT":[53],"FINDINGS:":[54],"Recent":[55,200],"reports":[56],"solidify":[57],"requirement":[59],"PI(3)K/Akt":[62],"pathway":[63],"hypertrophy.":[69],"In":[70],"response":[71],"to":[72,81,110,136,156,225],"IGF-1,":[73],"Akt":[74,100,107,227],"activates":[75],"downstream":[76],"effectors,":[77],"mTOR":[78],"p70S6K":[80],"stimulate":[82],"protein":[83],"thereby":[85],"increasing":[86],"cytoplasmic":[88],"compartment":[89],"fibers.":[92],"Tsc2":[93],"was":[94,125,134],"also":[95,164],"identified":[96],"as":[97,166],"a":[98,167],"novel":[99],"target,":[101],"whose":[102],"phosphorylation":[103],"inactivation":[105],"may":[108,235],"lead":[109],"an":[111],"increase":[112],"cell":[114,201],"size.":[115,222],"The":[116,160],"mechanisms":[117,187,211],"which":[119,189,213],"functions":[121,165],"wasting":[124],"recently":[126],"explored":[127],"using":[128],"in-vitro":[129],"assays":[130],"myogenesis.":[132],"Myostatin":[133],"found":[135],"repress":[137],"myogenesis":[138,171],"inhibiting":[140,173],"activity":[144],"MyoD.":[146,174],"Paradoxically,":[147],"expression":[149],"itself":[151],"regulated":[152],"MyoD":[154],"binding":[155],"promoter.":[159],"transcription":[162],"factor":[163],"negative":[168],"regulator":[169],"Chronic":[175],"activation":[176],"has":[179],"been":[180],"associated":[181,240],"with":[182,241],"wasting,":[184],"but":[185],"occurs":[192],"remain":[193],"most":[196],"unknown.":[198],"SUMMARY:":[199],"culture":[202],"animal":[204],"studies":[205],"have":[206],"provided":[207],"insight":[208],"on":[209],"Akt,":[214],"myostatin,":[215],"signaling":[218,228],"regulate":[220],"Clinical":[223],"intervention":[224],"boost":[226],"modulate":[230],"activities":[234],"prove":[236],"useful":[237],"diseases":[239],"chronic":[242],"wasting.":[244]},"counts_by_year":[{"year":2026,"cited_by_count":1},{"year":2024,"cited_by_count":1},{"year":2023,"cited_by_count":2},{"year":2021,"cited_by_count":2},{"year":2020,"cited_by_count":2},{"year":2019,"cited_by_count":3},{"year":2018,"cited_by_count":5},{"year":2017,"cited_by_count":1},{"year":2016,"cited_by_count":4},{"year":2015,"cited_by_count":8},{"year":2014,"cited_by_count":7},{"year":2013,"cited_by_count":13},{"year":2012,"cited_by_count":7}],"updated_date":"2026-11-06T12:05:46.655746","created_date":"2016-06-24T00:00:00"}