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Stimulation of protein kinase C modulates insulin-like growth factor-1- induced Akt activation in PC12 cells
Zheng W.-H.; Kar S.; Quirion R.
2000-05-05
Source PublicationJournal of Biological Chemistry
ISSN00219258
Volume275Issue:18Pages:13377-13385
Abstract

Activation of protein kinase C (PKC) plays an important role in the negative regulation of receptor signaling, but its effect on insulin-like growth factor-1 (IGF-1) receptor signaling remains unclear. In this study, we characterized the intracellular pathways involved in IGF-1-induced activation of Akt and evaluated the effects of the PKC activator phorbol 12-myristate 13-acetate (PMA) on the Akt activation by IGF-1. IGF-1 induced a time- and concentration-dependent activation of Akt. The effect of IGF-1 was blocked by the phosphatidylinositide 3-kinase (PI3K) inhibitors LY294002 (50 μM) and wortmannin (0.5 μM), but not by the MEK inhibitor PD98059 (50 μM) or the p70 S6 kinase pathway inhibitor rapamycin (50 nM), suggesting that the stimulation of Akt by IGF-1 is mediated by the PI3K pathway. Interestingly, cotreatment with PMA (400 nM) attenuated IGF-1-induced activation of Akt. The attenuation was blocked completely by the PKC inhibitor GO6983 (0.5 μM), but only partially by the MEK inhibitor PD98059 (50 μM), indicating that MAPK- dependent and -independent pathways are involved. PMA induced the activation of PKC in PC12 cells, and this induction was blocked by GO6983. These data further support the role of PKC in the effect of PMA. Moreover, PKCδ is likely involved in the action of PMA on the basis of data obtained using isoform-specific inhibitors such as rottlerin. PMA also decreased IGF-1- induced tyrosine phosphorylation of insulin receptor substrate-1 and its association with PI3K. Taken together, these results suggest, for the first time, that stimulation of PKC modulates IGF-1-induced activation of Akt.

DOI10.1074/jbc.275.18.13377
URLView the original
Indexed BySCI
WOS Research AreaBiochemistry & Molecular Biology
WOS SubjectBiochemistry & Molecular Biology
WOS IDWOS:000086925300033
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被引频次[WOS]:59   [WOS记录]     [WOS相关记录]
Document TypeJournal article
专题Faculty of Health Sciences
AffiliationDouglas Hospital Research Center
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Zheng W.-H.,Kar S.,Quirion R.. Stimulation of protein kinase C modulates insulin-like growth factor-1- induced Akt activation in PC12 cells[J]. Journal of Biological Chemistry,2000,275(18):13377-13385.
APA Zheng W.-H.,Kar S.,&Quirion R..(2000).Stimulation of protein kinase C modulates insulin-like growth factor-1- induced Akt activation in PC12 cells.Journal of Biological Chemistry,275(18),13377-13385.
MLA Zheng W.-H.,et al."Stimulation of protein kinase C modulates insulin-like growth factor-1- induced Akt activation in PC12 cells".Journal of Biological Chemistry 275.18(2000):13377-13385.
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