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Enhanced Akt phosphorylation and myogenic differentiation in PI3K p110β-deficient myoblasts is mediated by PI3K p110α and mTORC2.
MedLine Citation:
PMID:  23137199     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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:
Ronald W Matheny; Christine M Lynch; Luis A Leandry
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-9
Journal Detail:
Title:  Growth factors (Chur, Switzerland)     Volume:  -     ISSN:  1029-2292     ISO Abbreviation:  Growth Factors     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9000468     Medline TA:  Growth Factors     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Military Performance Division, US Army Research Institute of Environmental Medicine 15 Kansas Street, Building 42, Natick, MA 01760 , USA.
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