Cross-linking of surface IgM stimulates the Ras/Raf-1/MEK/MAPK cascade in human B lymphocytes - PubMed (original) (raw)

. 1994 Mar 11;269(10):7538-43.

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

A Tordai et al. J Biol Chem. 1994.

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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 p90rsk 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 p90rsk activation in these cells.

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