胰岛素受体
IRS1
胰岛素降解酶
生物
S-亚硝基化
胰岛素受体底物
生物化学
胰岛素
胰岛素抵抗
GRB10型
IRS2
酶
内分泌学
半胱氨酸
作者
Haoli Zhou,Zachary W. Grimmett,Nicholas M. Venetos,Colin T. Stomberski,Zhaoxia Qian,McLaughlin Pj,Paramjit S. Bansal,Rongli Zhang,James D. Reynolds,Richard T. Premont,Jonathan S. Stamler
出处
期刊:Cell
[Elsevier]
日期:2023-12-01
卷期号:186 (26): 5812-5825.e21
被引量:2
标识
DOI:10.1016/j.cell.2023.11.009
摘要
Summary
Acyl-coenzyme A (acyl-CoA) species are cofactors for numerous enzymes that acylate thousands of proteins. Here, we describe an enzyme that uses S-nitroso-CoA (SNO-CoA) as its cofactor to S-nitrosylate multiple proteins (SNO-CoA-assisted nitrosylase, SCAN). Separate domains in SCAN mediate SNO-CoA and substrate binding, allowing SCAN to selectively catalyze SNO transfer from SNO-CoA to SCAN to multiple protein targets, including the insulin receptor (INSR) and insulin receptor substrate 1 (IRS1). Insulin-stimulated S-nitrosylation of INSR/IRS1 by SCAN reduces insulin signaling physiologically, whereas increased SCAN activity in obesity causes INSR/IRS1 hypernitrosylation and insulin resistance. SCAN-deficient mice are thus protected from diabetes. In human skeletal muscle and adipose tissue, SCAN expression increases with body mass index and correlates with INSR S-nitrosylation. S-nitrosylation by SCAN/SNO-CoA thus defines a new enzyme class, a unique mode of receptor tyrosine kinase regulation, and a revised paradigm for NO function in physiology and disease.
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