Regulation of cell growth by IL-2: Role of STAT5 in protection from apoptosis but not in cell cycle progression

José Zamorano, Helen Y. Wang, Rouxiang Wang, Yufang Shi, Gregory D. Longmore, Achsah D. Keegan

Research output: Contribution to journalArticle

81 Scopus citations

Abstract

Cytokines play an essential role in the regulation of lymphocyte survival and growth. We have analyzed the pathways activated by IL-2 that lead to protection from apoptosis and cell proliferation. IL-2 can act as a long-term growth factor in 32D cells expressing the wild-type human (hu)IL- 2Rβ. By contrast, cells expressing a truncated form of the huIL-2Rβ, which is able to induce Bcl-2 and c-myc expression but not STAT5 activation, were not protected cell cycle progression in cells hearing the truncated huIL- 2Rβ with percentage of viable cells in the G0/G1, S, and G2/M phases similar to cells expressing the wild-type huIL-2Rβ. Transplantation of a region from the erythropoietin receptor, which contains a docking site for STAT5 (Y343) to the truncated huIL-2Rβ, restored the ability of IL-2 to signal both activation of STAT5 and protection from apoptosis. By contrast, transplantation of a region from the huIL-4Rα containing STAT6 docking sites did not confer protection from apoptosis. These results indicate that the IL- 2-induced cell cycle progression can be clearly distinguished from protection from apoptosis and that STAT5 participate in the regulation of apoptosis.

Original languageEnglish
Pages (from-to)3502-3512
Number of pages11
JournalJournal of Immunology
Volume160
Issue number7
StatePublished - Apr 1 1998

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