T-lymphocyte proliferation: tyrosine kinases in interleukin 2 signal transduction

Rosemarie Schmandt, Marion Fung, Naomichi Arima, Nan Zhang, Bernadine Leung, Christopher May, Spencer Gibson, Mary Hill, Warner Green, Gordon B. Mills

    Research output: Contribution to journalArticle

    12 Scopus citations

    Abstract

    Interleukin 2 (IL-2)-induced tyrosine phosphorylation appears to play a major role in IL-2-induced cellular proliferation. Several intracellular substrates including the β chain of the IL-2 receptor complex (IL-2Rβ), raf, MAP2 kinase, the regulatory 83kDa subunit of phosphatidylinositol-3 kinase and S6 kinases are substrates for the IL-2 receptor activated kinase(s). However, none of the identified members of the IL-2 receptor complex exhibits intrinsic tyrosine kinase activity. Therefore, the IL-2R complex must activate intracellular tyrosine kinases. We have demonstrated that specific tyrosine and serine/threonine kinases are coprecipitated with IL-2 receptor constructs that mediate IL-2-induced cell proliferation but not with those that do not. The IL-2-activated tyrosine kinase appears to be associated with a serine and proline rich intracellular domain which is highly conserved between IL-2Rβ and the erythropoietin receptor. Although the responsible kinase has not been identified, lck, fyn, fgr, ltk, hck and lyn can be ruled out as obligatory mediators. Using methods to clone tyrosine kinases from T cells, we have identified potential candidate kinases, including several which had not been known to be expressed by T lymphocytes as well as several unique kinases which had not been previously identified in any cell type.

    Original languageEnglish (US)
    Pages (from-to)551-573
    Number of pages23
    JournalBailliere's Clinical Haematology
    Volume5
    Issue number3
    DOIs
    StatePublished - Jan 1 1992

    ASJC Scopus subject areas

    • Hematology

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  • Cite this

    Schmandt, R., Fung, M., Arima, N., Zhang, N., Leung, B., May, C., Gibson, S., Hill, M., Green, W., & Mills, G. B. (1992). T-lymphocyte proliferation: tyrosine kinases in interleukin 2 signal transduction. Bailliere's Clinical Haematology, 5(3), 551-573. https://doi.org/10.1016/S0950-3536(11)80007-7