Differences in phosphorylation of the IL-2R associated JAK/STAT proteins between HTLV-I (+), IL-2-independent and IL-2-dependent cell lines and uncultured leukemic cells from patients with adult T-cell lymphoma/leukemia

被引:28
作者
Zhang, QA
Lee, B
Korecka, M
Li, G
Weyland, C
Eck, S
Gessain, A
Arima, N
Lessin, SR
Shaw, LM
Luger, S
Kamoun, M
Wasik, MA
机构
[1] Univ Penn Ctr, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA
[2] Univ Penn Ctr, Dept Hematol Oncol, Philadelphia, PA 19104 USA
[3] Univ Penn Ctr, Dept Dermatol, Philadelphia, PA 19104 USA
[4] Inst Pasteur, Paris, France
[5] Kagoshima Univ, Kagoshima 890, Japan
基金
美国国家卫生研究院;
关键词
IL-2R signaling; malignant T cells; JAK5; kinase; STAT; 5; protein; SHP-1; phosphatase;
D O I
10.1016/S0145-2126(98)00173-8
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
To determine activation status of the IL-2R-associated (Jak/STAT) pathway in the HTLV-I infected cells, we examined tyrosine phosphorylation of Jak3, STAT3, and STAT5 in several HTLV-I (+) T-cell lines and in uncultured leukemic T cells isolated from patients with adult T-cell lymphoma/leukemia (ATLL). Constitutive basal phosphorylation of Jak3 and, usually, STAT3 and STAT5 was detected in all four IL-2-independent cell lines tested, but in none of the three IL-2-dependent cell lines. Similarly, there was no detectable basal phosphorylation of Jak3 and STAT5 in the leukemic cells from ATLL patients (0/8 and 0/3, respectively). However, stimulation with IL-2 resulted in Jak3 and STAT5 phosphorylation in both leukemic ATLL cells and IL-2-dependent lines. Furthermore? expression of SHP-1 phosphatase which is a negative regulator of cytokine receptor signaling, was lost in most IL-2 independent cell Tines (3/4) but not in the leukemic ATLL cells (0/3). Finally, the HTLV-I (+) T-cell lines (313) but not the control, HTLV-I (-)T-cell lines were resistant to rapamycin and its novel analog RAD. We conclude that (1) HTLV-I infection per se does not result in a constitutive phosphorylation of the Jak3, STAT3, and STAT5 proteins; (2) malignant transformation in at least some cases of ATLL does not require the constitutive, but may require IL-2-induced, activation of the IL-2R Jak/STAT pathway; and (3) there are major differences in T-cell immortalization mechanism(s) which appear to involve SHP-1 and target molecules for rapamycin and RAD. (C) 1999 Published by Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:373 / 384
页数:12
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