Cross-linking of surface IgM stimulates the Ras/Raf-1/MEK/MAPK cascade in human B lymphocytes

Attila Tordai, Richard A. Franklin, Hiren Patel, Anne M. Gardner, Gary L. Johnson, Erwin W. Gelfand

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Abstract

The mechanism by which mitogen-activated protein kinase (MAPK) is activated in human B cells following cross-linking of the antigen receptor was investigated. Following anti-IgM antibody and phorbol 12-myristate 13- acetate (PMA) stimulation, we demonstrate the activation of Ras, Raf-1, and MAPK/ERK kinase (MEK), all of which are thought to participate in an important signaling cascade that leads to MAPK activation. We detected the kinase activities of Raf-1 and MEK toward purified recombinant substrates for each in this pathway (MEK for Raf-1 and MAPK for MEK). Following stimulation with either anti-IgM or PMA, Ras activation was observed, and the ability of Raf-1 to phosphorylate recombinant kinase-inactive MEK was increased by approximately 10-fold. Similarly, MEK activity toward kinase-active or - inactive recombinant MAPK also increased upon anti-IgM or PMA treatment. Furthermore, the activation of both MAPK and p90(rsk) was demonstrated under identical conditions in the B cells. We conclude that activation of B lymphocytes through the antigen receptor stimulates distinct members of the Ras/Raf-1/MEK cascade and this mechanism is likely to be responsible for MAPK and p90(rsk) activation in these cells.

Original languageEnglish
Pages (from-to)7538-7543
Number of pages6
JournalJournal of Biological Chemistry
Volume269
Issue number10
Publication statusPublished - Mar 11 1994

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Tordai, A., Franklin, R. A., Patel, H., Gardner, A. M., Johnson, G. L., & Gelfand, E. W. (1994). Cross-linking of surface IgM stimulates the Ras/Raf-1/MEK/MAPK cascade in human B lymphocytes. Journal of Biological Chemistry, 269(10), 7538-7543.