Phosphorylation of insulin receptor substrate‐1 serine 307 correlates with JNK activity in atrophic skeletal muscle

FEBS Letters

Graves, Lee M²  Hilder, Thomas L²  Grindeland, Richard E³  Tou, Janet C.L¹  Wade, Charles E³ 

[1] Wyle Laboratories, NASA Ames Research Center, Life Sciences Division, MS 239-11, Moffett Field, CA 94035, USA;Department of Pharmacology, University of North Carolina, CB#7365, Chapel Hill, NC 27599-7365, USA;NASA Ames Research Center, Life Sciences Division, MS 239-11, Moffett Field, CA 94035, USA

关键词: Skeletal muscle atrophy;    Hindlimb suspension;    Insulin resistance;    Insulin receptor substrate;    c-Jun NH2-terminal kinase;    AMB;    ambulatory;    Gastroc;    gastrocnemius;    GLUT4;    glucose transporter-4;    GSK-3β;    glycogen synthase kinase-3β;    HLS;    hindlimb suspended;    IRS;    insulin receptor substrate;    JNK;    c-Jun NH2-terminal kinase;   

DOI  :  10.1016/S0014-5793(03)00972-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

c-Jun NH₂-terminal kinase (JNK) has been shown to negatively regulate insulin signaling through serine phosphorylation of residue 307 within the insulin receptor substrate-1 (IRS-1) in adipose and liver tissue. Using a rat hindlimb suspension model for muscle disuse atrophy, we found that JNK activity was significantly elevated in atrophic soleus muscle and that IRS-1 was phosphorylated on Ser³⁰⁷ prior to the degradation of the IRS-1 protein. Moreover, we observed a corresponding reduction in Akt activity, providing biochemical evidence for the development of insulin resistance in atrophic skeletal muscle.

【 授权许可】

Unknown