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 Mills

Research output: Contribution to journalArticle

12 Citations (Scopus)

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

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Interleukin-2 Receptors
Signal Transduction
T-Lymphocytes
Phosphotransferases
Protein-Tyrosine Kinases
Interleukin-2
raf Kinases
Cell Proliferation
Phosphatidylinositol 3-Kinase
Ribosomal Protein S6 Kinases
Erythropoietin Receptors
Protein-Serine-Threonine Kinases
Proline
Serine
Tyrosine
emt protein-tyrosine kinase
Clone Cells
Phosphorylation

ASJC Scopus subject areas

  • Hematology

Cite this

T-lymphocyte proliferation : tyrosine kinases in interleukin 2 signal transduction. / Schmandt, Rosemarie; Fung, Marion; Arima, Naomichi; Zhang, Nan; Leung, Bernadine; May, Christopher; Gibson, Spencer; Hill, Mary; Green, Warner; Mills, Gordon.

In: Bailliere's Clinical Haematology, Vol. 5, No. 3, 01.01.1992, p. 551-573.

Research output: Contribution to journalArticle

Schmandt, R, Fung, M, Arima, N, Zhang, N, Leung, B, May, C, Gibson, S, Hill, M, Green, W & Mills, G 1992, 'T-lymphocyte proliferation: tyrosine kinases in interleukin 2 signal transduction', Bailliere's Clinical Haematology, vol. 5, no. 3, pp. 551-573. https://doi.org/10.1016/S0950-3536(11)80007-7
Schmandt, Rosemarie ; Fung, Marion ; Arima, Naomichi ; Zhang, Nan ; Leung, Bernadine ; May, Christopher ; Gibson, Spencer ; Hill, Mary ; Green, Warner ; Mills, Gordon. / T-lymphocyte proliferation : tyrosine kinases in interleukin 2 signal transduction. In: Bailliere's Clinical Haematology. 1992 ; Vol. 5, No. 3. pp. 551-573.
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