Antigen Activation of Mitogen-Activated Protein Kinase in Mast Cells Through Protein Kinase C-Dependent and Independent Pathways

Cheng Zhang, Noriyasu Hirasawa, Michael A. Beaven

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)

Abstract

We demonstrate discrete pathways for activation of mitogen-activated protein (MAP) kinase in cultured RBL-2H3 mast cells through protein kinase C (PKC), cytosolic calcium, and a third pathway that provides sustained signals for activation in Ag-stimulated cells. Thus, p42 MAP kinase was activated by increasing intracellular free Ca2+ with thapsigargin or by stimulating PKC with PMA. The latter stimulation was selectively blocked by the protein kinase C inhibitor, Ro31-7549. Stimulation of p42 MAP kinase by Ag resulted in relatively sustained activation of MAP kinase which was only partially suppressed by Ro31-7549. Kinetic studies revealed two components of the MAP kinase response to Ag: a rapid but transient component that was Ro31-7549 sensitive and presumably PKC dependent; and a more sustained component that was Ro31-7549 resistant and presumably PKC independent. Similarly, Ro31-7549 inhibited the early but not late release of arachidonic acid, a finding that was consistent with the known regulation of phospholipase A2 by MAP kinase. Early tyrosine phosphorylation events which were thought to be essential for Ag-induced activation of p42 MAP kinase and release of arachidonic acid were unaffected by Ro31-7549. The findings suggested that release of arachidonic acid was regulated primarily through MAP kinase but that PKC may transiently influence this release, either directly or indirectly through MAP kinase.

Original languageEnglish
Pages (from-to)4968-4975
Number of pages8
JournalJournal of Immunology
Volume158
Issue number10
Publication statusPublished - 1997 May 15

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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