| First Author | Zeitlmann L | Year | 1998 |
| Journal | J Biol Chem | Volume | 273 |
| Issue | 25 | Pages | 15445-52 |
| PubMed ID | 9624129 | Mgi Jnum | J:48182 |
| Mgi Id | MGI:1266917 | Doi | 10.1074/jbc.273.25.15445 |
| Citation | Zeitlmann L, et al. (1998) T cell activation induced by novel gain-of-function mutants of Syk and ZAP-70. J Biol Chem 273(25):15445-52 |
| abstractText | The Syk family tyrosine kinases play a crucial role in antigen receptor-mediated signal transduction, but their regulation and cellular targets remain incompletely defined. Following receptor engagement, phosphorylation of tyrosine residues within ZAP-70 and Syk is thought to control both kinase activity and recruitment of modulatory factors. We report here the characterization of novel mutants of ZAP-70 and Syk, in which conserved C-terminal tyrosine residues have been replaced by phenylalanines (ZAP YF-C, Syk YF-C). Both mutant kinases display a prominent gain-of-function phenotype in Jurkat T cells, as demonstrated by lymphokine promoter activation, tyrosine phosphorylation of potential targets in vivo, and elevated intracellular calcium mobilization. While the presence of p56-Lck was required for ZAP YF-C- induced signaling, Syk YF-C showed enhanced functional activity in Lck-deficient JCaM1 Jurkat cells. Our results implicate the C terminus of Syk family kinases as an important regulatory region modulating T cell activation. |
