title: Regulation of cell growth by IL-2: role of STAT5 in protection from apoptosis but not in cell cycle progression.
abstract: Cytokines play an essential role in the regulation of lymphocyte survival and growth. We have analyzed the pathways activated by IE-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-2R beta. By contrast, cells expressing a truncated form of the huIL-2R beta, 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-2R beta with percentages of viable cells in the G0/G1, S, and G2/M phases similar to cells expressing the wild-type huIL-2R beta. Transplantation of a region from the erythropoietin receptor, which contains a docking site for STAT5 (Y343) to the truncated huIL-2R beta, 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 alpha 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.
authors.affiliation: Department of Immunology, Jerome Holland Laboratories, American Red Cross, Rockville, MD 20855, USA.
authors.forename: J
authors.initials: J
authors.lastname: Zamorano
authors.forename: H Y
authors.initials: HY
authors.lastname: Wang
authors.forename: R
authors.initials: R
authors.lastname: Wang
authors.forename: Y
authors.initials: Y
authors.lastname: Shi
authors.forename: G D
authors.initials: GD
authors.lastname: Longmore
authors.forename: A D
authors.initials: AD
authors.lastname: Keegan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D002453:Cell Cycle / Q000187:drug effects / Q000276:immunology*; D002455:Cell Division / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000502:physiology*; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism / Q000502:physiology*; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D014407:Tumor Cells, Cultured
chemical_list: D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D017346:Protein Serine-Threonine Kinases