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Ataxia telangiectasia mutated (ATM) is required in insulin‐like growth factor‐1 (IGF‐1) signaling through the PI3K/Akt pathway
Author(s) -
Ching James Kain,
Luebbert Stephen H.,
Zhang Zhihong,
Marupudi Nandhini,
Banerjee Sankha,
Hurd Robin,
Collins Roy L.,
Ralston Lyle,
Fisher Jonathan S.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.782.3
Subject(s) - protein kinase b , p70 s6 kinase 1 , pi3k/akt/mtor pathway , phosphorylation , myogenesis , c2c12 , microbiology and biotechnology , small hairpin rna , signal transduction , cancer research , biology , chemistry , gene knockdown , myocyte , cell culture , genetics
Reports that ATM is required for full activation of Akt raise the hypothesis that ATM plays a role in IGF‐1 signaling through the PI3K/Akt pathway. Differentiated C2C12 cells harboring either ATM‐targeting shRNA or non‐targeting shRNA and myotubes from a C2C12 lineage previously exposed to empty vector lentivirus were incubated in the presence or absence of 10 nM IGF‐1. Western blot analysis showed that IGF‐1 stimulated phosphorylation of Akt S473, Akt T308, and p70 S6 kinase (S6K) in cells expressing non‐targeting shRNA and in empty vector controls, but the IGF‐1 effects were significantly reduced in cells with shRNA‐mediated ATM knockdown. Consistent with these findings, the ATM inhibitor KU55933 (10 μM) prevented stimulation of S6K phosphorylation in C2C12 myotubes exposed to IGF‐1. Furthermore, IGF‐1‐stimulated phosphorylation of Akt S473, Akt T308, and S6K was lower in isolated soleus muscles from mice expressing only one functional ATM allele (ATM +/‐) compared to muscles from wild‐type (ATM +/+) mice. Our data suggest that ATM is a modulator of IGF‐1 signaling through the Akt pathway. This work is supported by NICHD/NCMRR through a Pilot Project award from the National Skeletal Muscle Research Center.