RGD Reference Report - Phosphorylation of Tyr342 in the linker region of Syk is critical for Fc epsilon RI signaling in mast cells. - Rat Genome Database

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Phosphorylation of Tyr342 in the linker region of Syk is critical for Fc epsilon RI signaling in mast cells.

Authors: Zhang, J  Berenstein, E  Siraganian, RP 
Citation: Zhang J, etal., Mol Cell Biol 2002 Dec;22(23):8144-54.
RGD ID: 730070
Pubmed: PMID:12417718   (View Abstract at PubMed)
PMCID: PMC134060   (View Article at PubMed Central)

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 epsilon RI-mediated signaling. Antigen stimulation resulted in Tyr342 phosphorylation in mast cells. Syk with Y342F mutation failed to reconstitute Fc epsilon 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-gamma2, 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 epsilon 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.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
regulation of immune response  IDA 730070 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Syk  (spleen associated tyrosine kinase)


Additional Information