{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T14:48:41Z","timestamp":1791470921738,"version":"4.3.4"},"reference-count":60,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Endocrinology and Metabolism"],"published-print":{"date-parts":[[2013,7,15]]},"abstract":"<jats:p>\n                    Focal adhesion kinase (FAK) is an attachment complex protein associated with the regulation of muscle mass through as-of-yet unclear mechanisms. We tested whether FAK is functionally important for muscle hypertrophy, with the hypothesis that FAK knockdown (FAK-KD) would impede cell growth associated with a trophic stimulus. C\n                    <jats:sub>2<\/jats:sub>\n                    C\n                    <jats:sub>12<\/jats:sub>\n                    skeletal muscle cells harboring FAK-targeted (FAK-KD) or scrambled (SCR) shRNA were created using lentiviral transfection techniques. Both FAK-KD and SCR myotubes were incubated for 24 h with IGF-I (10 ng\/ml), and additional SCR cells (\u00b1IGF-1) were incubated with a FAK kinase inhibitor before assay of cell growth. Muscle protein synthesis (MPS) and putative FAK signaling mechanisms (immunoblotting and coimmunoprecipitation) were assessed. IGF-I-induced increases in myotube width (+41 \u00b1 7% vs. non-IGF-I-treated) and total protein (+44 \u00b1 6%) were, after 24 h, attenuated in FAK-KD cells, whereas MPS was suppressed in FAK-KD vs. SCR after 4 h. These blunted responses were associated with attenuated IGF-I-induced FAK Tyr\n                    <jats:sup>397<\/jats:sup>\n                    phosphorylation and markedly suppressed phosphorylation of tuberous sclerosis complex 2 (TSC2) and critical downstream mTOR signaling (ribosomal S6 kinase, eIF4F assembly) in FAK shRNA cells (all P &lt; 0.05 vs. IGF-I-treated SCR cells). However, binding of FAK to TSC2 or its phosphatase Shp-2 was not affected by IGF-I or cell phenotype. Finally, FAK-KD-mediated suppression of cell growth was recapitulated by direct inhibition of FAK kinase activity in SCR cells. We conclude that FAK is required for IGF-I-induced muscle hypertrophy, signaling through a TSC2\/mTOR\/S6K1-dependent pathway via means requiring the kinase activity of FAK but not altered FAK-TSC2 or FAK-Shp-2 binding.\n                  <\/jats:p>","DOI":"10.1152\/ajpendo.00541.2012","type":"journal-article","created":{"date-parts":[[2013,5,22]],"date-time":"2013-05-22T01:04:44Z","timestamp":1369184684000},"page":"E183-E193","source":"Crossref","is-referenced-by-count":82,"title":["Focal adhesion kinase is required for IGF-I-mediated growth of skeletal muscle cells via a TSC2\/mTOR\/S6K1-associated pathway"],"prefix":"10.1152","volume":"305","author":[{"given":"Hannah","family":"Crossland","sequence":"first","affiliation":[{"name":"Medical Research Council-Arthritis Research United Kingdom Centre of Excellence for Musculoskeletal Ageing Research, School of Graduate Entry Medicine and Health, University of Nottingham, Royal Derby Hospital, Derby, United Kingdom;"},{"name":"School of Sport, Exercise, and Health Sciences, Loughborough University, Loughborough, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abid A.","family":"Kazi","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles H.","family":"Lang","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James A.","family":"Timmons","sequence":"additional","affiliation":[{"name":"School of Sport, Exercise, and Health Sciences, Loughborough University, Loughborough, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Pierre","sequence":"additional","affiliation":[{"name":"Centre d'Immunologie de Marseille-Luminy, Aix-Marseille Universit\u00e9, Marseille, France;"},{"name":"Institut National de la Sante et de la Recherche Medicale, Marseille, France; and"},{"name":"Centre National de la Recherche Scientifique, Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Wilkinson","sequence":"additional","affiliation":[{"name":"Medical Research Council-Arthritis Research United Kingdom Centre of Excellence for Musculoskeletal Ageing Research, School of Graduate Entry Medicine and Health, University of Nottingham, Royal Derby Hospital, Derby, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Smith","sequence":"additional","affiliation":[{"name":"Medical Research Council-Arthritis Research United Kingdom Centre of 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