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Fiber type‐specific regulation of the Akt substrate of 160 kDa (AS160) in mouse skeletal muscle
Author(s) -
Taylor Eric B.,
Kramer Henning F.,
Fujii Nobuharu L.,
Yu Haiyan,
Roeckl Katja S.C.,
Witczak Carol A.,
Sano Hiroyuki,
Peter Lauren E.,
Hirshman Michael F.,
Lienhard Gustav E.,
Goodyear Laurie J.
Publication year - 2007
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.21.6.a1207-b
Subject(s) - skeletal muscle , protein kinase b , ampk , chemistry , phosphorylation , glucose uptake , medicine , endocrinology , microbiology and biotechnology , protein kinase a , biology , insulin , biochemistry
AS160 phosphorylation has recently emerged as a critical regulatory step in contraction‐ and insulin‐stimulated glucose uptake in skeletal muscle. Mice express a long and short AS160 splice‐variant differing by a single exon. Using PCR we determined that skeletal muscle expresses 17‐fold more long form than short form AS160 mRNA. With cell free assays we found that two putative AS160 kinases in skeletal muscle, AMP‐activated protein kinase (AMPK) and Akt, directly phosphorylate the AS160 long form. To compare fiber type‐specific AS160 regulation, we used soleus (SOL, rich in type I fibers), gastrocnemius (GAS, both type II and I), and tibialis anterior (TA, predominantly type II) muscles. Relative AS160 protein expression was greatest in SOL (2.3 ± 0.08) compared to GAS (1.0 ± 0.03) and TA (0.45 ± 0.04). In contrast, AS160 phosphorylation in response to in vivo treatment with AICAR (AMPK activator) or insulin was greatest in TA [ AICAR : TA (1.8 ± 0.06); GAS (1.3 ± 0.03); SOL (1.09 ± 0.17), Insulin : TA (2.1 ± 0.2); GAS (1.9 ± 0.3); SOL (1.8 ± 0.3)]. Thus, type II fibers have an increased ratio of AS160 phosphorylation to AS160 protein expression. We conclude that the AS160 long form is the predominant splice‐variant expressed in skeletal muscle, and that AMPK and Akt are AS160 kinases. Fiber‐type is a key determinant of AS160 phosphorylation in skeletal muscle. Support: NIH F32 DK07851, R01DK25336, R01AR42238