TY - JOUR
T1 - T-lymphocyte proliferation
T2 - tyrosine kinases in interleukin 2 signal transduction
AU - Schmandt, Rosemarie
AU - Fung, Marion
AU - Arima, Naomichi
AU - Zhang, Nan
AU - Leung, Bernadine
AU - May, Christopher
AU - Gibson, Spencer
AU - Hill, Mary
AU - Green, Warner
AU - Mills, Gordon B.
PY - 1992
Y1 - 1992
N2 - 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.
AB - 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.
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U2 - 10.1016/S0950-3536(11)80007-7
DO - 10.1016/S0950-3536(11)80007-7
M3 - Article
C2 - 1457964
AN - SCOPUS:0026658278
SN - 0950-3536
VL - 5
SP - 551
EP - 573
JO - Bailliere's Clinical Haematology
JF - Bailliere's Clinical Haematology
IS - 3
ER -