p21(ras) mediates control of IL-2 gene promoter function in T cell activation

S. I. Rayter, M. Woodrow, S. C. Lucas, D. A. Cantrell, J. Downward

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    165 Citations (Scopus)


    It has been shown previously in T cells that stimulation of protein kinase C or the T cell antigen receptor leads to a rapid and persistent activation of p21(ras) as measured by a dramatic increase in the amount of bound GTP. These stimuli are also known to induce the expression of the T lymphocyte growth factor, interleukin-2 (IL-2), an essential growth factor for the immune system. Receptor induced activation of p21(ras) has been demonstrated in several cell types but involvement of protein kinase C as an upstream activator of p21(ras) appears to be unique to T cells. In this study we show that p21(ras) acts as a component of the protein kinase C and T cell antigen receptor downstream signalling pathway controlling IL-2 gene expression. In the murine T cell line EL4, constitutively active p21(ras) greatly potentiates the phorbol ester and T cell receptor agonist induced production of IL-2 as measured both by biological assay for the cytokine and by the use of a reporter construct. Active p21(ras) also partially replaces the requirement for protein kinase C activation in synergizing with a calcium ionophore to induce production of IL-2. Furthermore, using a dominant negative mutant of ras, Ha-rasN17, we show that endogenous ras function is essential for induction of IL-2 expression in response to protein kinase C or T cell receptor stimulation. Activation of ras proteins is thus a necessary but not sufficient event in the induction of IL-2 synthesis. Ras proteins are therefore pivotal signalling molecules in T cell activation.

    Original languageEnglish
    Pages (from-to)4549-4556
    Number of pages8
    JournalEMBO Journal
    Issue number12
    Publication statusPublished - 1 Jan 1992


    • IL-2 gene
    • p21(ras)
    • Promoter function
    • T cell activation

    ASJC Scopus subject areas

    • General Neuroscience
    • Molecular Biology
    • General Biochemistry,Genetics and Molecular Biology
    • General Immunology and Microbiology


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