| Autor: |
Chen XH; Laboratory of Cellular and Molecular Biology, NCI, National Institutes of Health, Bethesda, Maryland 20892-4255, USA., Patel BK, Wang LM, Frankel M, Ellmore N, Flavell RA, LaRochelle WJ, Pierce JH |
| Jazyk: |
angličtina |
| Zdroj: |
The Journal of biological chemistry [J Biol Chem] 1997 Mar 07; Vol. 272 (10), pp. 6556-60. |
| DOI: |
10.1074/jbc.272.10.6556 |
| Abstrakt: |
The Jak1, Jak2, Jak3, and Fes tyrosine kinases have been demonstrated to undergo tyrosine phosphorylation in response to interleukin (IL)-4 stimulation in different cell systems. However, it is not clear which, if any, of these kinases are responsible for initiating IL-4-induced tyrosine phosphorylation of intracellular substrates in vivo. In the present study, we have utilized a mutant Jak1-deficient HeLa cell line, E1C3, and its parental Jak1-expressing counterpart, 1D4, to analyze the role of Jak1 in mediating IL-4-induced tyrosine phosphorylation events. IL-4 treatment rapidly induced tyrosine phosphorylation of insulin receptor substrate (IRS)-1 and IRS-2 in 1D4 but not in E1C3 cells. IL-4-mediated tyrosine phosphorylation of Stat6 was pronounced in 1D4 cells, while no IL-4-induced Stat6 phosphorylation was detected in E1C3 cells. IL-4 also induced Stat6 DNA binding activity from lysates of 1D4 but not E1C3 cells utilizing a radiolabeled immunoglobulin heavy chain germline epsilon promotor sequence (Iepsilon) in an electrophoretic mobility shift assay. Reconstitution of Jak1 expression in E1C3 cells restored the ability of IL-4 to induce IRS and Stat6 tyrosine phosphorylation. These results provide evidence that Jak1 expression is required for mediating tyrosine phosphorylation and activation of crucial molecules involved in IL-4 signal transduction. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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