| Autor: |
Czyzyk JK; Division of Rheumatology and Immunology, Thurston Arthritis Research Center, Chapel Hill, NC 27599-7280, USA., Fernsten PD, Brtva TR, Der CJ, Winfield JB |
| Jazyk: |
angličtina |
| Zdroj: |
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 1998 Feb 13; Vol. 243 (2), pp. 444-50. |
| DOI: |
10.1006/bbrc.1998.8114 |
| Abstrakt: |
Protein kinase C (PKC)-dependent activation of the Ras signal transduction cascade is essential for induction of the IL-2 promoter during stimulation of T lymphocytes via the T cell receptor (TCR). In this study, the effects of PKC-activating phorbol myristate acetate (PMA) on Ras-dependent activation of transcription from the ets/AP-1 Ras-responsive promoter element were examined in human T cells. Pretreatment of Jurkat cells with the Src-family PTK inhibitor herbimycin A resulted in a 50% inhibition of transactivation of the reporter following incubation with PMA. Evidence was also obtained to suggest the participation of the leukocyte-specific protein tyrosine phosphatase CD45, a regulator of Src-like PTKs, in the PMA-induced activation of the Ras/Raf pathway. First, PMA-induced transactivation of ets/AP-1 is diminished 75% in CD45-negative variants, compared with CD45-positive cells. Second, engagement of CD45 by monoclonal antibodies suppresses the PMA response from the reporter construct. Taken together, these data suggest that Src-related proteins mediate PKC-dependent activation of the Ras/Raf pathway and implicate CD45 in the TCR-independent activation of T lymphocytes induced by agents such as PMA. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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