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

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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.

Original languageEnglish
Pages (from-to)371-377
Number of pages7
JournalBiochemical and Biophysical Research Communications
Issue number2
Publication statusPublished - Jan 10 2003

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Kaburagi, Y., Satoh, S., Yamamoto-Honda, R., Ito, Y., Akanuma, Y., Sekihara, H., Yasuda, K., Sasazuki, T., Kadowaki, T., & Yazaki, Y. (2003). Protection of insulin receptor substrate-3 from staurosporine-induced apoptosis. Biochemical and Biophysical Research Communications, 300(2), 371-377.