CD45 and Src-related protein tyrosine kinases regulate the T cell response to phorbol esters

Jan K. Czyzyk, Philip D. Fernsten, Teresa R. Brtva, Channing J. Der, John B. Winfield

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)444-450
Number of pages7
JournalBiochemical and Biophysical Research Communications
Issue number2
StatePublished - Feb 13 1998

Bibliographical note

Funding Information:
This work was supported in part by National Institutes of Health Grants AR30863, AR7416, and AR3070.


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