Protection of insulin receptor substrate-3 from staurosporine-induced apoptosis

Yasushi Kaburagi; Shinobu Satoh; Ritsuko Yamamoto-Honda; Yuzuru Ito; Yasuo Akanuma; Hisahiko Sekihara; Kazuki Yasuda; Takehiko Sasazuki; Takashi Kadowaki; Yoshio Yazaki

doi:10.1016/s0006-291x(02)02855-3

Protection of insulin receptor substrate-3 from staurosporine-induced apoptosis

Biochem Biophys Res Commun. 2003 Jan 10;300(2):371-7. doi: 10.1016/s0006-291x(02)02855-3.

Authors

Yasushi Kaburagi¹, Shinobu Satoh, Ritsuko Yamamoto-Honda, Yuzuru Ito, Yasuo Akanuma, Hisahiko Sekihara, Kazuki Yasuda, Takehiko Sasazuki, Takashi Kadowaki, Yoshio Yazaki

Affiliation

¹ The Department of Metabolic Disorder, Research Institute, International Medical Center of Japan, 1-12-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan. [email protected]

PMID: 12504093
DOI: 10.1016/s0006-291x(02)02855-3

Abstract

In primary adipocytes, insulin receptor substrate (IRS)-1 and -3 are expressed in a comparable amount and play distinct roles in insulin signaling. To examine the roles of these IRS in apoptosis inhibition, we evaluated staurosporine-induced apoptosis in Chinese hamster ovary (CHO) cells overexpressing human insulin receptor and IRS-1 or IRS-3. Overexpression of both IRS protected CHO cells from staurosporine-induced apoptosis. Overexpressed IRS-3 as well as IRS-1 enhanced phosphoinositide (PI) 3-kinase activity in response to insulin and increased phosphorylation of protein kinase B (PKB) at S473 and phosphorylation of one of the members of the forkhead transcription factor FKHRL1 on T32 in both insulin-untreated and -treated states. Treatment of these cells with a PI 3-kinase inhibitor LY294002 suppressed apoptosis-inhibitory effects of IRS-1 and IRS-3 as well as the phosphorylation of PKB and FKHRL1. These results indicate that both IRS-1 and IRS-3 take part in apoptosis inhibition through the PI 3-kinase/PKB/forkhead cascade.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis*
CHO Cells
Cell Survival / drug effects
Chromones / pharmacology
Cricetinae
DNA-Binding Proteins / metabolism
Dose-Response Relationship, Drug
Enzyme Inhibitors / pharmacology
Insulin / pharmacology
Insulin Receptor Substrate Proteins
Morpholines / pharmacology
Phosphoinositide-3 Kinase Inhibitors
Phosphoproteins / genetics
Phosphoproteins / physiology*
Protein Serine-Threonine Kinases*
Proto-Oncogene Proteins / metabolism
Proto-Oncogene Proteins c-akt
Receptor, Insulin / genetics
Staurosporine / antagonists & inhibitors
Staurosporine / pharmacology*
Transcription Factors / metabolism
Transfection

Substances

Chromones
DNA-Binding Proteins
Enzyme Inhibitors
IRS1 protein, human
Insulin
Insulin Receptor Substrate Proteins
Morpholines
Phosphoinositide-3 Kinase Inhibitors
Phosphoproteins
Proto-Oncogene Proteins
Transcription Factors
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Receptor, Insulin
Protein Serine-Threonine Kinases
Proto-Oncogene Proteins c-akt
Staurosporine