Regular Article
CD45 and Src-Related Protein Tyrosine Kinases Regulate the T Cell Response to Phorbol Esters

https://doi.org/10.1006/bbrc.1998.8114Get rights and content

Abstract

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.

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    • Cited by (0)

    1

    Current address: Department of Pathology, Yale University, 20 York St., East Pavilion Room 2-608, P.O. Box 208070, New Haven, CT 06520-8070.

    2

    Current address: Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109.

    3

    To whom correspondence should be addressed at Thurston Arthritis Research Center, 3330 Thurston Building, CB #7280, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7280. Fax: 919-966-1739. E-mail:[email protected].

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