Premium
Membrane localization of all class I PI 3‐kinase isoforms suppresses c‐Myc‐induced apoptosis in Rat1 fibroblasts via Akt
Author(s) -
Link Wolfgang,
Rosado Aranzazu,
Fominaya Jesus,
Thomas James E.,
Carnero Amancio
Publication year - 2005
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.20479
Subject(s) - gene isoform , phosphoinositide 3 kinase , microbiology and biotechnology , protein kinase b , signal transduction , receptor tyrosine kinase , kinase , phosphorylation , apoptosis , heterotrimeric g protein , pi3k/akt/mtor pathway , chemistry , wortmannin , tyrosine phosphorylation , tyrosine kinase , receptor , biology , g protein , biochemistry , gene
Phosphoinositide 3′‐kinases (PI3Ks) constitute a family of lipid kinases implicated in signal transduction through tyrosine kinase receptors and heterotrimeric G protein‐linked receptors. PI3Ks are heterodimers made up of four different 110‐kDa catalytic subunits (p110α, p110β, p110γ, and p110δ) and a smaller regulatory subunit. Despite a clear implication of PI3Ks in survival signaling, the contribution of the individual PI3K isoforms has not been elucidated. To address this issue, we generated Rat1 fibroblasts that co‐express c‐Myc and membrane targeted derivates of the different p110 isoforms. Here we present data for the first time showing that activation of PI3‐kinase signaling through membrane localization of p110β, p110γ, and p110δ protects c‐Myc overexpressing Rat1 fibroblasts from apoptosis caused by serum deprivation like it has been described for p110α. Expression of each p110 isoform reduces significantly caspase‐3 like activity in this apoptosis model. Decreased caspase‐3 activity correlates with the increase in Akt phosphorylation in cells that contain one of the myristoylated p110 isoforms. p110 isoform‐mediated protection from cell death was abrogated upon expression of a kinase‐negative version of Akt. © 2005 Wiley‐Liss, Inc.