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Molecular and Cellular Biology, December 2001, p. 8318-8328, Vol. 21, No. 24
Institute of Molecular Genetics, Academy of
Sciences of the Czech Republic, 14220 Prague, Czech
Republic,1 and Molecular
Inflammation Section, National Institute of Arthritis and
Musculoskeletal and Skin Diseases, National Institutes of Health,
Bethesda, Maryland 20892-18202
Received 23 July 2001/Accepted 14 September 2001
The first step in immunoreceptor signaling is represented by
ligand-dependent receptor aggregation, followed by receptor
phosphorylation mediated by tyrosine kinases of the Src family.
Recently, sphingolipid- and cholesterol-rich plasma membrane
microdomains, called lipid rafts, have been identified and proposed to
function as platforms where signal transduction molecules may interact
with the aggregated immunoreceptors. Here we show that aggregation of
the receptors with high affinity for immunoglobulin E (Fc
0270-7306/01/$04.00+0 DOI: 10.1128/MCB.21.24.8318-8328.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Structure-Function Analysis of Lyn Kinase Association with Lipid
Rafts and Initiation of Early Signaling Events after Fc
Receptor
I Aggregation
ová,1,2
RI) in mast
cells is accompanied by a co-redistribution of the Src family kinase Lyn. The co-redistribution requires Lyn dual fatty acylation, Src
homology 2 (SH2) and/or SH3 domains, and Lyn kinase activity, in
cis or in trans. Palmitoylation site-mutated
Lyn, which is anchored to the plasma membrane but exhibits reduced
sublocalization into lipid rafts, initiates the tyrosine
phosphorylation of Fc
RI subunits, Syk protein tyrosine kinase, and
the linker for activation of T cells, along with an increase in the
concentration of intracellular Ca2+. However, Lyn mutated
in both the palmitoylation and myristoylation sites does not anchor to
the plasma membrane and is incapable of initiating Fc
RI
phosphorylation and early signaling events. These data, together with
our finding that a constitutively tyrosine-phosphorylated Fc
RI does
not exhibit an increased association with lipid rafts, suggest that
Fc
RI phosphorylation and early activation events can be initiated
outside of lipid rafts.
*
Corresponding author. Mailing address: NIAMS/NIH,
Building 10, Room 9N228, MSC 1820, Bethesda, MD 20892-1820. Phone:
(301) 496-7592. Fax: (301) 402-0012. E-mail:
juan_rivera{at}nih.gov.
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