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J Biol Chem, Vol. 273, Issue 49, 32934-32942, December 4, 1998
From the Laboratory of Experimental Immunology, The murine Ly49 family contains nine genes in two
subgroups: the inhibitory receptors (Ly49A, B, C, E, F, G2, and I) and
the noninhibitory receptors (Ly49D and H). Unlike their inhibitory counterparts, Ly49D and H do not contain immunoreceptor tyrosine-based inhibitory motifs but associate with a recently described co-receptor, DAP12, to transmit positive signals to natural killer (NK) cells. DAP12
is also expressed in myeloid cells, but the receptors coupled to it
there are unknown. Here we document the signaling pathways of the
Ly49D/DAP12 complex in NK cells. We show that ligation of Ly49D results
in 1) tyrosine phosphorylation of several substrates, including
phospholipase C
DAP12-mediated Signal Transduction in Natural Killer Cells
A DOMINANT ROLE FOR THE Syk PROTEIN-TYROSINE KINASE
, Intramural
Research Support Program,
1, Cbl, and p44/p42 mitogen-activated protein kinase,
and 2) calcium mobilization. Moreover, we demonstrate that although
human DAP12 reportedly binds the SH2 domains of both Syk and Zap-70,
ligation of Ly49D leads to activation of Syk but not Zap-70. Consistent
with this observation, Ly49D/DAP12-mediated calcium mobilization is
blocked by dominant negative Syk but not by catalytically inactive
Zap-70. These data demonstrate the dependence of DAP12-coupled
receptors on Syk and suggest that the outcome of Ly49D/DAP12 engagement
will be regulated by Cbl and culminate in the activation of
transcription factors.
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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