IL-2 and IL-7 induce heterodimerization of STAT5 isoforms in human peripheral blood T lymphoblasts.
Despite differences in T cell responses induced by interleukin (IL)-2 and IL-7, both cytokines modulate T cell functions by activation of signal transducers and activators of transcription (STAT) proteins. We examined the contribution of the two isoforms of STAT5, STAT5A and STAT5B, to IL-2- and IL-7-induced activation of human peripheral blood T lymphoblasts. Both cytokines induced assembly of STAT5A and STAT5B containing complexes capable of binding to the interferon-gamma activation sequence (GAS), and these complexes rapidly translocated (within 1 min) into the nucleus of IL-2- or IL-7-treated cells. The kinetics of this translocation were delayed in IL-7-treated as compared to IL-2-treated cells. IL-2 and IL-7 were equivalent in their ability to induce tyrosine phosphorylation of STAT5A and STAT5B and to facilitate binding of these STATs to an immobilized GAS element. Both IL-2 and IL-7 induced substantial amounts of STAT5A/STAT5B heterodimerization. Moreover, we observed constitutive association of STAT3 with each STAT5 isomer. These data suggest that IL-2 and IL-7 induce assembly of STAT heterodimers in a similar manner and that subsequent cellular responses may be driven by induction of similar sets of genes.
Rosenthal
L A
LA
Division of Cytokine Biology, Food and Drug Administration, Bethesda, Maryland 20892-4555, USA.
Winestock
K D
KD
Finbloom
D S
DS
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D019281:Dimerization; D004591:Electrophoresis, Polyacrylamide Gel; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D015851:Interleukin-7 / Q000494:pharmacology*; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008894:Milk Proteins; D011401:Promoter Regions, Genetic / Q000235:genetics; D055503:Protein Multimerization / Q000187:drug effects; D011994:Recombinant Proteins / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D050799:STAT5 Transcription Factor; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D015534:Trans-Activators / Q000737:chemistry / Q000378:metabolism*; D025521:Tumor Suppressor Proteins
D004268:DNA-Binding Proteins; D007376:Interleukin-2; D015851:Interleukin-7; D007527:Isoenzymes; D008894:Milk Proteins; D011994:Recombinant Proteins; D050799:STAT5 Transcription Factor; C494092:STAT5A protein, human; C494095:STAT5B protein, human; C494093:Stat5a protein, mouse; C494096:Stat5b protein, mouse; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins; D004247:DNA