EGF or PDGF receptors activate atypical PKC lambda through phosphatidylinositol 3-kinase

Overexpression of a TPA-insensitive PKC member, an atypical protein kinase C (aPKC lambda), results in an enhancement of the transcriptional activation of TPA response element (TRE) in cells stimulated with epidermal growth factor (EGF) or platelet-derived growth factor (PDGF). EGF or PDGF also caused a transient increase in the in vivo phosphorylation level and a change in the intracellular localization of aPKC lambda from the nucleus to the cytosol, indicating the activation of aPKC lambda in response to this growth factor stimulation. These immediate signal-dependent changes in aPKC lambda were observed for a PDGF receptor add-back mutant (Y40/51) that possesses only two of the five major autophosphorylation sites and binds PI3-kinase, and were inhibited by wortmannin, an inhibitor of PI3-kinase. Furthermore, an N-terminal fragment of the catalytic subunit of PI3-kinase, p110 alpha, inhibited aPKC lambda-dependent activation of TRE in Y40/51 cells stimulated with PDGF. Overexpression of p110 alpha resulted in an enhancement of TRE expression in response to PDGF and the regulatory domain of aPKC lambda inhibited this TRE activation in Y40/51 cells. These results provide the first in vivo evidence supporting the presence of a novel signalling pathway from receptor tyrosine kinases to aPKC lambda through PI3-kinase.