title: Enhanced Akt phosphorylation and myogenic differentiation in PI3K p110β-deficient myoblasts is mediated by PI3K p110α and mTORC2.
abstract: Phosphoinositide 3-kinase (PI3K) is a principal regulator of Akt activation and myogenesis; however, the function of PI3K p110β in these processes is not well defined. To address this, we investigated the role of p110β in Akt activation and skeletal muscle cell differentiation. We found that Akt phosphorylation was enhanced in p110β-deficient myoblasts in response to Insulin-like Growth Factor-I (IGF-I), epidermal growth factor, or p110α overexpression, as compared to p110β-sufficient cells. This effect was associated with increased mammalian target of rapamycin complex 2 activation, even in myoblasts deficient in mSin1 and rictor. Conversely, in response to the G-protein-coupled receptor agonist lysophosphatidic acid, Akt phosphorylation was attenuated in p110β-deficient myoblasts. Loss of p110β also enhanced the expression of myogenic markers at the myoblast stage and during the first 48 h of differentiation. These data demonstrate that reductions in p110β are associated with agonist-specific Akt hyperactivation and accelerated myogenesis, thus revealing a negative role for p110β in Akt activation and during myoblast differentiation.
authors.affiliation: Military Performance Division, US Army Research Institute of Environmental Medicine, 15 Kansas Street, Building 42, Natick, MA 01760, USA. ronald.matheny@us.army.mil
authors.forename: Ronald W
authors.initials: RW
authors.lastname: Matheny
authors.forename: Christine M
authors.initials: CM
authors.lastname: Lynch
authors.forename: Luis A
authors.initials: LA
authors.lastname: Leandry
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D058543:Class Ia Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008246:Lysophospholipids / Q000378:metabolism; D000076225:Mechanistic Target of Rapamycin Complex 2; D046912:Multiprotein Complexes / Q000378:metabolism*; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000378:metabolism; D032446:Myoblasts / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D012038:Regeneration; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D058543:Class Ia Phosphatidylinositol 3-Kinase; D007334:Insulin-Like Growth Factor I; D008246:Lysophospholipids; D000076225:Mechanistic Target of Rapamycin Complex 2; D046912:Multiprotein Complexes; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D034741:RNA, Small Interfering; D058570:TOR Serine-Threonine Kinases; C032881:lysophosphatidic acid