期刊
CELLULAR SIGNALLING
卷 17, 期 7, 页码 881-890出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2004.11.008
关键词
pertussis toxin; G(i/o) proteins; PC12 cells; nerve growth factor; Akt
类别
In G alpha(z)-deficient mice, survival of sympathetic neurons is significantly attenuated in the presence of pertussis toxin (PTX). This suggests that G(i/o). proteins may have distinct roles in neuronal survival. Here, we investigated the possible involvement of G(i/o) proteins in nerve growth factor (NGF)-induced pro-survival phosphatidylinositol-3-kinase (PI3K)/Akt signaling in rat pheochromocytoma PC12 cells. Treatment of PC12 cells with NGF increased the Akt phosphorylation level in a time- and dose-dependent manner. The NGF-dependent Akt activation was partially attenuated by PTX or overexpression of regulators of G protein signaling Z1 (RGSZ1) and G alpha-interacting protein (GAIP)), indicating the participation of G(i/o) proteins. In contrast, epidermal growth factor (EGF)-mediated Akt phosphorylation was unaffected by PTX or RGSZ1 and GAIP. Expression of PTX-resistant mutants of G alpha(i1), G alpha(i3), G alpha(oA), and G alpha(oB), but not G alpha(i2), abolished the inhibitory effect of PTX on NGF-induced Akt activation. The use of transducin as a G beta gamma scavenger further revealed that G beta gamma subunits rather than Ga-i/o acted as the signal transducer. The activation profiles of Akt-regulated downstream effectors such as Bad, IKK, and nuclear factor-kappa B (NF kappa B) were also examined. NGF-stimulated phosphorylation of Bad and IKK and transcriptional activity of NF kappa B were indeed sensitive to treatments with PTX. This is the first study that demonstrates the involvement of G(i/o) proteins in NGF-induced Akt signaling. (c) 2004 Elsevier Inc. All rights reserved.
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