ACTIVATION OF TRANSCRIPTIONAL FACTORS STAT5 AND STAT3
DURING HUMAN T-LYMPHOCYTE PROLIFERATION INDUCED BY DIFFERENT MITOGENIC STIMULI
I. A. Karitskaya,1 N. D. Aksenov, V. V. Zenin, A. L. Khaidukova, I. I. Marakhova
Institute of Cytology, RAS, St. Petersburg;
1 e-mail: inkar74@mail.ru
The activation of closely related transcription factors STAT5α and STAT5β is one of the key signalling
events during interleukin-2-dependent stage of T-lymphocyte proliferation. Here, we investigate the activation
of STAT5 and STAT3 family proteins on different stages of T-cell proliferative response to various mitogenic
stimuli. The activation of STAT proteins was estimated according to their tyrosine phosphorylation. Isolated peripheral
blood lymphocytes were stimulated by phytogemagglutinin (PHA), or by phorbol-12,13-dibutyrate
(PDBu) with calcium ionophore — ionomycin, or by exogenous interleukin-2 (IL-2). After activation of T-cells
by PHA as well as by PDBu with ionomycin we observed phosphorylation of STAT5 not earlier than in 5 h. The
maximum phosphorylation (by 10 times and more, as compared to control resting lymphocytes) was detected
following 24 h of mitogen stimulation. In the lymphocytes pretreated by PHA in submitogenic concentration,
exogenous IL-2 induces a proliferative response. High phosphorylation level of STAT5 was determined 10 min
after addition of IL-2 and kept for the next 24 h. In contrast to STAT5, some basal phosphorylation of STAT3
was found in resting and PHA-pretreated T-cells. The profile of phosphorylation STAT3 during mitogen-induced
activation is more leveled. An immunosuppressant cyclosporine A taken at antiproliferative concentration
decreased phosphorylation of both STAT5 and STAT3 by 1.5—2.0 times at early stages, as well as at late stages
of activation. A correlation between alteration in tyrosine phosphorylation level of STAT5 and the expression of
the high affinity IL-5 receptor was established. Taken together, we report that the increased STAT5 phosphorylation
can serve as a marker of T-lymphocyte entrance into IL-2-dependent stage of proliferation after T-cell activation
by different mitogens.
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