TY - JOUR
T1 - Protection of insulin receptor substrate-3 from staurosporine-induced apoptosis
AU - Kaburagi, Yasushi
AU - Satoh, Shinobu
AU - Yamamoto-Honda, Ritsuko
AU - Ito, Yuzuru
AU - Akanuma, Yasuo
AU - Sekihara, Hisahiko
AU - Yasuda, Kazuki
AU - Sasazuki, Takehiko
AU - Kadowaki, Takashi
AU - Yazaki, Yoshio
N1 - Funding Information:
This work was supported by a grant for diabetes research (MF-4) from the Organization for Pharmaceutical Safety and Research (to Y.K.), Grant No. 13670540 from the Japanese Ministry of Education, Science, Culture and Sport (to S.S.), and Kihara Memorial Yokohama Foundation for the Advancement of Life Sciences (to S.S.).
PY - 2003/1/10
Y1 - 2003/1/10
N2 - 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.
AB - 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.
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U2 - 10.1016/S0006-291X(02)02855-3
DO - 10.1016/S0006-291X(02)02855-3
M3 - Article
C2 - 12504093
AN - SCOPUS:12144286481
SN - 0006-291X
VL - 300
SP - 371
EP - 377
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -