@entity442 ( @entity442 ) and @entity2690 are known to prevent apoptosis. The signaling network of @entity442 and @entity2690 occurs via multiple pathways involving different @entity8277 substrates (IRSs). To define their roles in the anti-apoptotic function of @entity442 and @entity2690 , we established brown pre-adipocyte cell lines from wild-type and IRS knockout (KO) animals. In response to 16 h of serum deprivation, @entity10175 -deficient cells showed a significant decrease in response to @entity442 protection from apoptosis, whereas no changes were observed in the @entity21320 , @entity68935 , or @entity27020 KO cells. Five hours after serum withdrawal, cells already began to undergo apoptosis. At this early time point, @entity442 and @entity2690 were able to protect both wild-type and @entity10175 KO cells from death by 85-90%. After a longer period of serum deprivation, the protective ability of @entity2690 and @entity442 was decreased, and this was especially reduced in the @entity10175 KO cells. Reconstitution of these cells with @entity10175 , @entity21320 , @entity68935 , or @entity10175 / @entity21320 chimeras restored the anti-apoptotic effects of @entity442 , whereas overexpression of @entity27020 had no effect at long time points and actually reduced the effect of @entity442 at the short time point. The biochemical basis of the defect in anti-apoptosis was not dependent on phosphorylation of mitogen-activated protein kinase; whereas phosphoinositide 3-kinase activity was decreased by 30% in @entity10175 KO cells. Akt phosphorylation was slightly reduced in these cells. Phosphorylation of the transcription factors @entity268 response element-binding protein and @entity4012 by @entity442 and @entity2690 was markedly reduced in @entity10175 KO cells. In addition, both @entity442 and @entity2690 prevented @entity522 cleavage in the wild-type cells, and this effect was greatly reduced in the @entity10175 -deficient cells. These findings suggest that the IRS proteins may play differential roles in the anti-apoptotic effects of @entity442 and @entity2690 in brown pre-adipocytes, with @entity10175 being predominant, possibly acting through @entity522 -, @entity10366 -, and @entity4012 -dependent mechanisms.

Differential roles of XXXX substrates in the anti-apoptotic function of insulin-like growth factor-1 and insulin.

@entity27020 :: ('8471', 'Gene') :: ['IRS-4'] @entity268 :: ('CHEBI:17489', 'Chemical') :: ['cAMP'] @entity10175 :: ('3667', 'Gene') :: ['IRS-1'] @entity522 :: ('836', 'Gene') :: ['caspase-3'] @entity442 :: ('3479', 'Gene') :: ['Insulin-like growth factor-1', 'IGF-1'] @entity2690 :: ('3630', 'Gene') :: ['insulin'] @entity68935 :: ('442338', 'Gene') :: ['IRS-3'] @entity8277 :: ('3643', 'Gene') :: ['insulin receptor'] @entity10366 :: ('1385', 'Gene') :: ['CREB'] @entity4012 :: ('2308', 'Gene') :: ['FKHR'] @entity21320 :: ('8660', 'Gene') :: ['IRS-2']
@entity8277 :: (3643,Gene) :: ['insulin receptor']
