Phosphorylation of Syk Activation Loop Tyrosines Is Essential for Syk Function
| Autor: | Reuben P. Siraganian, Melvin L. Billingsley, Juan Zhang, Randall L. Kincaid |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
inorganic chemicals
Chemistry Kinase Syk hemic and immune systems Tyrosine phosphorylation Cell Biology environment and public health Biochemistry In vitro Cell biology enzymes and coenzymes (carbohydrates) chemistry.chemical_compound bacteria Phosphorylation Tyrosine Kinase activity Molecular Biology Histamine |
| Zdroj: | Journal of Biological Chemistry. 275:35442-35447 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m004549200 |
| Popis: | Syk is an important protein-tyrosine kinase in immunoreceptor signaling. FceRI aggregation in mast cells induces tyrosine phosphorylation and increased enzymatic activity of Syk. The two adjacent tyrosines in the Syk activation loop are thought to be important for the propagation of FceRI signaling. To evaluate the phosphorylation of these tyrosines in vivo and further understand the relationship of Syk tyrosine phosphorylation with its function, an antibody was developed specific for phosphorylated tyrosines in the activation loop of Syk. FceRI aggregation on mast cells induced the phosphorylation of both tyrosine residues of the activation loop. The kinase activity of Syk played the major role in phosphorylating its activation loop tyrosines both in vivoand in vitro. In FceRI-stimulated mast cells, the total Syk tyrosine phosphorylation paralleled the phosphorylation of its activation loop tyrosines and downstream propagation of signals for histamine release. In contrast, the cell surface binding of anti-ganglioside monoclonal antibody AA4 induced only strong general tyrosine phosphorylation of Syk and minimal histamine release and weak phosphorylation of activation loop tyrosines. These results demonstrate that phosphorylation of the activation loop tyrosines is important for mediating receptor signaling and is a better marker of Syk function than is total Syk tyrosine phosphorylation. |
| Databáze: | OpenAIRE |
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