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Molecular and Cellular Biology, December 2001, p. 8318-8328, Vol. 21, No. 24
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 Fcepsilon Receptor I Aggregation

Martina Kovárová,1,2 Pavel Tolar,1 Ramachandran Arudchandran,2 Lubica Dráberová,1 Juan Rivera,2,* and Petr Dráber1

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 (Fcvarepsilon 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 Fcvarepsilon 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 Fcvarepsilon RI phosphorylation and early signaling events. These data, together with our finding that a constitutively tyrosine-phosphorylated Fcvarepsilon RI does not exhibit an increased association with lipid rafts, suggest that Fcvarepsilon 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.

Molecular and Cellular Biology, December 2001, p. 8318-8328, Vol. 21, No. 24
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.24.8318-8328.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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