C. Murga et al., A novel role for phosphatidylinositol 3-kinase beta in signaling from G protein-coupled receptors to Akt, J BIOL CHEM, 275(16), 2000, pp. 12069-12073
The protein kinase Akt plays a central role in a number of key biological f
unctions including protein synthesis, glucose homeostasis, and the regulati
on of cell survival or death, The mechanism by which tyrosine kinase growth
factor receptors stimulate Akt has been recently defined. In contrast, the
mechanism of activation of Akt by other cell surface receptors is much les
s understood. For G protein-coupled receptors (GPCRs), conflicting data sug
gest that these receptors stimulate Akt in a cell type-specific manner by a
set to be fully elucidated mechanism. Here, we took advantage of the avail
ability of cells, where Akt activity could not be enhanced by agonists acti
ng on this large family of cell surface receptors, such as NIH 3T3 cells, t
o investigate the pathway linking GPCRs to Akt. We present evidence that ex
pression of phosphatidylinositol 3-kinase (PI3K) beta is necessary and suff
icient to transmit signals from G proteins to Akt in these murine fibroblas
ts and that the activation of PI3K beta may represent the most likely mecha
nism whereby GPCRs stimulate Akt, as the vast majority of cells do not expr
ess PI3K gamma, a known G protein-sensitive PI3K isoform. Furthermore, avai
lable evidence indicates that GPCRs activate Akt by a pathway distinct from
that utilized by growth factor receptors, as it involves the tyrosine phos
phorylation-independent activation of PI3K beta by G protein beta gamma dim
ers.