Neither the LCK nor the FYN kinases are obligatory for IL-2-mediated signal transduction in HTLV-l-infected human T cells

Gordon B. Mills, Naomichi Arima, Christopher May, Mary Hill, Rosemarie Schmandt, Jun Li, Nell G. Mlyamoto, Warner C. Greene

    Research output: Contribution to journalArticle

    24 Scopus citations

    Abstract

    IL-2 is one of the principal growth factors regulating the proliferation of T lymphocytes. Although two Independent IL-2-blnding molecules have been moleculariy cloned and shown to participate in the formation of a high affinity receptor complex, their primary structures do not suggest a specific mechanism for IL-2 growth signal transduction across the cell membrane. Neither IL-2 receptor subunit contains an intrinsic kinase domain; nevertheless, tyrosine phosphorylation of various intracellular substrates is one of the first biochemical changes observed following activation of the IL-2 receptor (IL-2R). Both serine/threonlne and tyrosine kinases can be co-preclpitated as part of the IL-2R complex suggesting that the IL-2 signalling may involve the activation of non-covalently associated intracellular kinases. However, controversy exists as to which kinases are involved in IL-2 signal transduction; in particular, which klnase(s) mediates the first or proximal event(s) In the signalling process. Activation of the IL-2R leads to serine and threonine phosphorylation of the SRC tyrosine kinase family member, LCK, and an increase in LCK tyrosine kinase activity. Furthermore, LCK can be co-fmmunopreclpltated with the β chain of the IL-2R indicating its association with the receptor complex. IL-2 has also been reported to Increase FYN kinase activity and to alter its association with the 85 kDa subunit of phosphatidylinosltol-3 kinase thus suggesting a role for FYN in IL-2 signal transduction. However, in this report, we now demonstrate that neither LCK nor FYN are obligatory for IL-2-induced growth of HTLV-l-lnfected human T cells. Lack of expression of LCK or FYN in the HTLV-I-Infected T cell lines was demonstrated by a combination of Northern blotting, polymerase chain reaction, Western blotting, and in vitro kinase activity. Despite the absence of LCK or FYN, IL-2 induced similar patterns of rapid tyrosine phosphorylation. Similar results were observed in cell lines lacking expression of the LYN, FGR, HCK, and LTK tyrosine kinases. Thus, none of these tyrosine kinases alone appears to be required for growth signalling through the IL-2R in the HTLV-l-lnfected T cell lines analyzed. The findings raise the possibility that an, as yet, unidentified tyrosine kinase is involved. Alternatively, this biological signalling system may exhibit remarkable redundancy whereby several different tyrosine kinases may be capable of associating with the IL-2R complex and mediating Intracellular signalling.

    Original languageEnglish (US)
    Pages (from-to)1233-1243
    Number of pages11
    JournalInternational Immunology
    Volume4
    Issue number11
    DOIs
    StatePublished - Nov 1 1992

    Keywords

    • FYN kinase
    • HTLV-I infection
    • IL-2
    • LCK kinase

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology

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