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J. Exp. Med.,
Volume 188, Number 7, October 5, 1998 1297-1306
By
From the * Department of Microbiology and the B cell antigen receptor (BCR) cross-linking activates three distinct families of nonreceptor protein tyrosine kinases (PTKs): src-family kinases, Syk, and Btk; these PTKs are responsible for initiating downstream events. BCR cross-linking in the chicken DT40 B cell line also activates
three distinct mitogen-activated protein kinases (MAPKs): extracellular signal-regulated kinase (ERK)2, c-jun NH2-terminal kinase (JNK)1, and p38 MAPK. To dissect the functional roles
of these PTKs in MAPK signaling, activation of MAPKs was examined in various PTK-deficient DT40 cells. BCR-mediated activation of ERK2, although maintained in Lyn-deficient
cells, was abolished in Syk-deficient cells and partially inhibited in Btk-deficient cells, indicating that BCR-mediated ERK2 activation requires Syk and that sustained ERK2 activation requires Btk. BCR-mediated JNK1 activation was maintained in Lyn-deficient cells but abolished in both Syk- and Btk-deficient cells, suggesting that JNK1 is activated via a Syk- and
Btk-dependent pathway. Consistent with this, BCR-mediated JNK1 activation was dependent
on intracellular calcium and phorbol myristate acetate-sensitive protein kinase Cs. In contrast,
BCR-mediated p38 MAPK activation was detected in all three PTK-deficient cells, suggesting
that no single PTK is essential. However, BCR-mediated p38 MAPK activation was abolished in Lyn/Syk double deficient cells, demonstrating that either Lyn or Syk alone may be sufficient
to activate p38 MAPK. Our data show that BCR-mediated MAPK activation is regulated at
the level of the PTKs.
Department of Immunology, University of
Washington, Seattle, Washington 98195; and the § Department of Molecular Genetics, Institute for
Liver Research, Kansai Medical University, Moriguchi 570, Japan
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