Alternative translation initiation of Caveolin-2 desensitizes insulin signaling through dephosphorylation of insulin receptor by PTP1B and causes insulin Check for resistance

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1864

Article

Kwon, Hayeong¹  Jang, Donghwan¹  Choi, Moonjeong¹  Lee, Jaewoong¹  Jeong, Kyuho¹  Pak, Yunbae¹ 

[1] Gyeongsang Natl Univ, Div Life Sci, Grad Sch Appl Life Sci, PMBBRC,Plus Program BK21, Jinju 52828, South Korea

关键词: Caveolin-2;    Alternative translation initiation;    Insulin receptor;    Protein tyrosine phosphatase 1B;    Lysosomal degradation;    Insulin resistance;   

DOI  :  10.1016/j.bbadis.2018.03.022

来源: Elsevier

【 摘 要 】

Insulin resistance, defined as attenuated sensitivity responding to insulin, impairs insulin action. Direct causes and molecular mechanisms of insulin resistance have thus far remained elusive. Here we show that alternative translation initiation (ATI) of Caveolin-2 (Cav-2) regulates insulin sensitivity. Cav-2 beta isoform yielded by ATI desensitizes insulin receptor (IR) via dephosphorylation by protein-tyrosine phosphatase 1B (PTP1B), and subsequent endocytosis and lysosomal degradation of IR, causing insulin resistance. Blockage of Cav-2 ATI protects against insulin resistance by preventing Cav-2 beta-PTP1B-directed IR desensitization, thereby normalizing insulin sensitivity and glucose uptake. Our findings show that Cav-2 beta is a negative regulator of IR signaling, and identify a mechanism causing insulin resistance through control of insulin sensitivity via Cav-2 ATI.

【 授权许可】

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