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Molecular and Cellular Biology, December 2002, p. 8144-8154, Vol. 22, No. 23
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.23.8144-8154.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Phosphorylation of Tyr342 in the Linker Region of Syk Is Critical for Fc{varepsilon}RI Signaling in Mast Cells

Juan Zhang,* Elsa Berenstein, and Reuben P. Siraganian

Receptors and Signal Transduction Section, Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892

Received 31 May 2002/ Returned for modification 29 July 2002/ Accepted 22 August 2002

The linker region of Syk and ZAP70 tyrosine kinases plays an important role in regulating their function. There are three conserved tyrosines in this linker region; Tyr317 of Syk and its equivalent residue in ZAP70 were previously shown to negatively regulate the function of Syk and ZAP70. Here we studied the roles of the other two tyrosines, Tyr342 and Tyr346 of Syk, in Fc{varepsilon}RI-mediated signaling. Antigen stimulation resulted in Tyr342 phosphorylation in mast cells. Syk with Y342F mutation failed to reconstitute Fc{varepsilon}RI-initiated histamine release. In the Syk Y342F-expressing cells there was dramatically impaired receptor-induced phosphorylation of multiple signaling molecules, including LAT, SLP-76, phospholipase C-{gamma}2, but not Vav. Compared to wild-type Syk, Y342F Syk had decreased binding to phosphorylated immunoreceptor tyrosine-based activation motifs and reduced kinase activity. Surprisingly, mutation of Tyr346 had much less effect on Fc{varepsilon}RI-dependent mast cell degranulation. An anti-Syk-phospho-346 tyrosine antibody indicated that antigen stimulation induced only a very minor increase in the phosphorylation of this tyrosine. Therefore, Tyr342, but not Tyr346, is critical for regulating Syk in mast cells and the function of these tyrosines in immune receptor signaling appears to be different from what has been previously reported for the equivalent residues of ZAP70.

* Corresponding author. Mailing address: RAST Section, OIIB, Bldg. 10, Rm. 1N106, NIDCR, NIH, Bethesda, MD 20892. Phone: (301) 496-5105. Fax: (301) 480-8328. E-mail: lzhang{at}dir.nidcr.nih.gov.

Molecular and Cellular Biology, December 2002, p. 8144-8154, Vol. 22, No. 23
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.23.8144-8154.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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