Oxygen tension regulates the stability of insulin receptor substrate-1 (IRS-1) through caspase-mediated cleavage SCIE SCOPUS

Cited 17 time in WEB OF SCIENCE Cited 18 time in Scopus
Title
Oxygen tension regulates the stability of insulin receptor substrate-1 (IRS-1) through caspase-mediated cleavage
Author(s)
Kang, Sung Gyun; Brown, Alexandra L.; Chung, Jay H.
KIOST Author(s)
Kang, Sung Gyun(강성균)
Publication Year
2007-03
Abstract
The insulin and insulin-like growth factor-1 (IGF-1) receptors mediate signaling for energy uptake and growth through insulin receptor substrates (IRSs), which interact with these receptors as well as with downstream effectors. Oxygen is essential not only for ATP production through oxidative phosphorylation but also for many cellular processes, particularly those involved in energy homeostasis. The oxygen tension in vivo is significantly lower than that in the air and can vary widely depending on the tissue as well as on perfusion and oxygen consumption. How oxygen tension affects IRSs and their functions is poorly understood. Our findings indicate that transient hypoxia (1% oxygen) leads to caspase-mediated cleavage of IRS-1 without inducing cell death. The IRS-1 protein level rebounds rapidly upon return to normoxia. Protein tyrosine phosphatases (PTPs) appear to be important for the IRS-1 cleavage because tyrosine phosphorylation of the insulin receptor was decreased in hypoxia and IRS-1 cleavage could be blocked either with H2O2 or with vanadate, each of which inhibits PTPs. Activity of Akt, a downstream effector of insulin and IGF-1 signaling that is known to suppress caspase activation, was suppressed in hypoxia. Overexpression of dominant-negative Akt led to IRS-1 cleavage even in normoxia, and overexpression of constitutively active Akt partially suppressed IRS-1 cleavage in hypoxia, suggesting that hypoxiamediated suppression of Akt may induce caspase-mediated IRS-1 cleavage. In conclusion, our study elucidates a mechanism by which insulin and IGF-1 signaling can be matched to the oxygen level that is available to support growth and energy metabolism.
ISSN
0021-9258
URI
https://sciwatch.kiost.ac.kr/handle/2020.kiost/4718
DOI
10.1074/jbc.M610659200
Bibliographic Citation
Journal of Biological Chemistry, v.282, no.9, pp.6090 - 6097, 2007
Publisher
American Society for Biochemistry and Molecular Biology Inc.
Type
Article
Language
English
Document Type
Article
Publisher
American Society for Biochemistry and Molecular Biology Inc.
Related Researcher
Research Interests

marine biotechnology,microbiology,해양생명공학,미생물학

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