Protein kinase C α, βI, and βII isozymes regulate cytokine production in mast cells through MEKK2/ERK5-dependent and -independent pathways

Guiming Li, Joseph J. Lucas, Erwin W. Gelfand

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Regulation of MAPK pathways by PKC isoforms was examined in murine bone marrow-derived mast cells (BMMCs). The PKCα, βI, and βII isoforms showed the most robust activation after FcεR1-mediated stimulation by anti-ovalbumin specific IgE and ovalbumin (IgE-ova). PKCα, βI, and βII were all involved in activation of JNK, MEKK2, and ERK5, with differential relative contributions of each isoform to specific MAPK pathway components. BMMCs from mice lacking MEKK2 showed reduced production (50-60%) of IL-6, IL-13, and TNF-α after stimulation, demonstrating MEKK2-dependent and -independent pathways for cytokine production. Cytokine production was stimulated by over-expression of PKC in cells from MEKK2-deficient and wild-type mice. Activation of ERK5 did not occur in BMMCs lacking MEKK2, indicating that MEKK2-independent cytokine production was also ERK5-independent. Since MAPK modules differentially regulate mast cell functions, including degranulation and cytokine production, it is suggested that specific functions could be targeted by inhibiting specific PKC isoforms.

Original languageEnglish (US)
Pages (from-to)10-18
Number of pages9
JournalCellular Immunology
Volume238
Issue number1
DOIs
StatePublished - Nov 1 2005

Keywords

  • Cytokines
  • Kinases
  • Mast cells

ASJC Scopus subject areas

  • Immunology

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