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 journalArticlepeer-review

13 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
Externally publishedYes

ASJC Scopus subject areas

  • Hematology

Fingerprint Dive into the research topics of 'T-lymphocyte proliferation: tyrosine kinases in interleukin 2 signal transduction'. Together they form a unique fingerprint.

Cite this