TY - JOUR
T1 - Regulation of cell growth by IL-2
T2 - Role of STAT5 in protection from apoptosis but not in cell cycle progression
AU - Zamorano, José
AU - Wang, Helen Y.
AU - Wang, Rouxiang
AU - Shi, Yufang
AU - Longmore, Gregory D.
AU - Keegan, Achsah D.
PY - 1998/4/1
Y1 - 1998/4/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0032055611&partnerID=8YFLogxK
M3 - Article
C2 - 9531312
AN - SCOPUS:0032055611
SN - 0022-1767
VL - 160
SP - 3502
EP - 3512
JO - Journal of Immunology
JF - Journal of Immunology
IS - 7
ER -