EGF or PDGF receptors activate atypical PKClambda through phosphatidylinositol 3‐kinase.

K Akimoto, R Takahashi, S Moriya, N Nishioka… - The EMBO …, 1996 - embopress.org
K Akimoto, R Takahashi, S Moriya, N Nishioka, J Takayanagi, K Kimura, Y Fukui, S Osada…
The EMBO journal, 1996embopress.org
Overexpression of a TPA‐insensitive PKC member, an atypical protein kinase C
(aPKClambda), 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 aPKClambda from the
nucleus to the cytosol, indicating the activation of aPKClambda in response to this growth …
Overexpression of a TPA‐insensitive PKC member, an atypical protein kinase C (aPKClambda), 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 aPKClambda from the nucleus to the cytosol, indicating the activation of aPKClambda in response to this growth factor stimulation. These immediate signal‐dependent changes in aKPClambda 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, p110alpha, inhibited aPKClambda‐dependent activation of TRE in Y40/51 cells stimulated with PDGF. Overexpression of p110alpha resulted in an enhancement of TRE expression in response to PDGF and the regulatory domain of aPKClambda 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 aPKClambda through PI3‐kinase.
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