Protein kinase C (PKC)η-mediated PKCμ activation modulates ERK and JNK signal pathways

Ilona Brändlin, Susanne Hübner, Tim Eiseler, Marina Martinez-Moya, Andreas Horschinek, Angelika Hausser, Gisela Link, Steffen Rupp, Peter Storz, Klaus Pfizenmaier, Franz Josef Johannes

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105 Scopus citations

Abstract

Protein kinase C (PKC), a family of lipid-activated serine kinases, is involved in multiple functions in the regulation of growth control. The PKC-related isoform PKCμ/PKD has been implicated in mitogenic signal cascades because of the activation of p42/p44 MAPK leading to Elk1-mediated gene transcription, and PKCμ/PKD has been shown to be activated via a PKC-dependent pathway. By using confocal analyses, we demonstrate here that PKCμ partially colocalizes with PKCη in different cell types. Colocalization depends on the presence of the PKCμ pleckstrin homology domain. Co-expression of constitutively active PKCη with PKCμ leads to a significant enhancement of the PKCμ substrate phosphorylation capacity as a result of an increased phosphorylation of the activation loop Ser738/742 of PKCμ, whereas Ser910 autophosphorylation remains unaffected. In vitro phosphorylation experiments show that PKCη directly phosphorylates PKCμ on activation loop serines. Consequently, the p42 MAPK cascade is triggered leading to an increase in reporter gene activity driven by a serum-responsive element in HEK293 cells. At the same time, PKCη-mediated JNK activation is reduced, providing evidence for a mutual regulation of PKCμ/PKCη affecting different arms of the p38/ERK/JNK pathways. Our data provide evidence for the sequential involvement of selective PKC isoforms in kinase cascades and identify the relevant domains in PKCμ for interaction with and activation by PKCη as pleckstrin homology domain and activation loop.

Original languageEnglish (US)
Pages (from-to)6490-6496
Number of pages7
JournalJournal of Biological Chemistry
Volume277
Issue number8
DOIs
StatePublished - Feb 22 2002

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Brändlin, I., Hübner, S., Eiseler, T., Martinez-Moya, M., Horschinek, A., Hausser, A., Link, G., Rupp, S., Storz, P., Pfizenmaier, K., & Johannes, F. J. (2002). Protein kinase C (PKC)η-mediated PKCμ activation modulates ERK and JNK signal pathways. Journal of Biological Chemistry, 277(8), 6490-6496. https://doi.org/10.1074/jbc.M106083200