EGF or PDGF receptors activate atypical PKClambda through phosphatidylinositol 3-kinase

EMBO J. 1996 Feb 15;15(4):788-98.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cell Compartmentation
  • Cells, Cultured
  • Chlorocebus aethiops
  • Enzyme Activation
  • ErbB Receptors / physiology*
  • Gene Expression
  • Humans
  • Molecular Sequence Data
  • Phosphatidylinositol 3-Kinases
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism*
  • Phosphotyrosine / metabolism
  • Protein Kinase C / metabolism*
  • RNA, Messenger / genetics
  • Rats
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Receptors, Platelet-Derived Growth Factor / physiology*
  • Regulatory Sequences, Nucleic Acid
  • Signal Transduction
  • Transcription, Genetic


  • RNA, Messenger
  • Phosphotyrosine
  • Phosphotransferases (Alcohol Group Acceptor)
  • ErbB Receptors
  • Receptor Protein-Tyrosine Kinases
  • Receptors, Platelet-Derived Growth Factor
  • Protein Kinase C