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Protein kinase C (PKC)eta-mediated PKC mu activation modulates ERK and JNK signal pathways

Ilona Brändlin1, Susanne Hübner, Tim Eiseler

  • 1Fraunhofer Institute for Interfacial Engineering, Nobelstrasse 12, University of Stuttgart, Allmandring 31, 70569 Stuttgart, Germany.

The Journal of Biological Chemistry
|December 14, 2001
PubMed

Insights

Protein Kinase C eta (PKC eta) directly activates PKC mu, enhancing its role in mitogenic signaling pathways. This PKC eta-mediated activation of PKC mu influences MAPK cascades, impacting gene transcription.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Signal Transduction

Background:

  • Protein Kinase C (PKC) isoforms are crucial lipid-activated serine kinases regulating cell growth.
  • PKC mu/PKD is implicated in mitogenic signaling, activating p42/p44 MAPK and Elk1-mediated transcription.
  • PKC mu activation occurs through a PKC-dependent pathway.

Purpose of the Study:

  • To investigate the interaction and functional relationship between PKC mu and PKC eta.
  • To elucidate the molecular mechanisms underlying PKC mu activation by PKC eta.
  • To understand the impact of this interaction on downstream signaling pathways.

Main Methods:

  • Confocal microscopy for analyzing protein colocalization.
  • Coexpression studies to assess kinase activity and substrate phosphorylation.
  • In vitro phosphorylation assays to determine direct interactions.
  • Reporter gene assays to measure transcriptional activity.

Main Results:

  • PKC mu partially colocalizes with PKC eta in various cell types, dependent on the PKC mu pleckstrin homology domain.
  • Active PKC eta enhances PKC mu substrate phosphorylation via direct activation loop phosphorylation.
  • PKC eta triggers the p42 MAPK cascade, increasing reporter gene activity.
  • PKC eta activation of PKC mu reduces JNK activation, indicating pathway crosstalk.

Conclusions:

  • PKC eta directly phosphorylates and activates PKC mu, enhancing its role in mitogenic signaling.
  • The pleckstrin homology domain and activation loop of PKC mu are critical for interaction and activation by PKC eta.
  • This cross-isoform regulation influences distinct arms of the p38/ERK/JNK signaling pathways.

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