Abstract
The two related protein‐tyrosine kinases Syk and Zap are rapidly phosphorylated on tyrosine residues and enzymatically activated upon crosslinking of the T cell antigen receptor. We have previously reported that the activation of Syk is less dependent on the Src family kinase Lck than the activation of Zap. Here we report that overexpression of Syk in the Lck‐negative JCaM1 cells enabled the T cell antigen receptor/CD3 complex to induce a normal activation of the mitogen‐activated protein kinase (MAPK) pathway and expression of a nuclear factor of activated T cells reporter construct. In contrast, Zap and other protein‐tyrosine kinases were unable to reconstitute these signaling pathways when expressed at the same levels. In parallel, Syk was phosphorylated on tyrosine, while Zap was not. The Syk‐mediated T cell antigen receptor‐induced MAPK activation was detectable within 1 min of receptor stimulation and peaked at 3–5 min. The capacity of Syk to reconstitute the MAPK response required the catalytic activity of Syk, an intact autophosphorylation site (Y518 and Y519), both Src homology 2 domains and it was blocked by the inhibitory N17‐mutated dominant‐negative Ras construct. A Y341→F mutant of Syk, which is deficient in its interaction with phospholipase Cγ1 and Vav, was less efficient than wild‐type Syk. Our results suggest that Syk, in contrast to Zap, can transduce signals from the T cell antigen receptor independently of Lck.
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Dates
Type | When |
---|---|
Created | 21 years, 1 month ago (July 16, 2004, 9:40 a.m.) |
Deposited | 1 year, 10 months ago (Oct. 16, 2023, 8:24 p.m.) |
Indexed | 4 months, 3 weeks ago (April 4, 2025, 1:09 p.m.) |
Issued | 28 years, 4 months ago (April 1, 1997) |
Published | 28 years, 4 months ago (April 1, 1997) |
Published Online | 21 years, 1 month ago (July 16, 2004) |
Published Print | 28 years, 4 months ago (April 1, 1997) |
@article{Williams_1997, title={Reconstitution of T Cell Antigen Receptor‐Induced Erk2 Kinase Activation in Lck‐Negative JCaM1 Cells by Syk}, volume={245}, ISSN={1432-1033}, url={http://dx.doi.org/10.1111/j.1432-1033.1997.00084.x}, DOI={10.1111/j.1432-1033.1997.00084.x}, number={1}, journal={European Journal of Biochemistry}, publisher={Wiley}, author={Williams, Scott and Couture, Clément and Gilman, Jennifer and Jascur, Thomas and Deckert, Marcel and Altman, Amnon and Mustelin, Tomas}, year={1997}, month=apr, pages={84–90} }