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*
Department of Immunology, Jerome Holland Laboratories, American Red Cross, Rockville, MD 20855; and
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110
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-2Rß. By contrast, cells expressing a truncated form of
the huIL-2Rß, which is able to induce Bcl-2 and c-myc
expression but not STAT5 activation, were not protected from apoptosis
by IL-2; consequently, they could not be grown long term in the
presence of IL-2. However, IL-2 promoted cell cycle progression in
cells bearing the truncated huIL-2Rß with percentages of
viable cells in the G0/G1, S, and
G2/M phases similar to cells expressing the wild-type
huIL-2Rß. Transplantation of a region from the erythropoietin
receptor, which contains a docking site for STAT5 (Y343) to the
truncated huIL-2Rß, 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-4R
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
participates in the regulation of apoptosis.
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