Interleukin 4-inducible phosphorylation of HMG-I(Y) is inhibited by rapamycin.

Wang DZ, Ray P, Boothby M
J Biol Chem. 1995 270 (39): 22924-32

PMID: 7559428 · DOI:10.1074/jbc.270.39.22924

The non-histone chromosomal protein HMG-I(Y) participates in repression of transcription directed by a promoter which confers interleukin 4 (IL-4)-inducible activation in transfected B cell lines. Metabolic labeling, phosphoamino acid analyses, and in vitro phosphorylation studies demonstrate that IL-4 induces serine phosphorylation of HMG-I(Y) in B lymphocytes. Phosphopeptide mapping shows that the predominant site of phosphorylation contains a casein kinase II consensus motif. The immunosuppressive agent rapamycin has been shown preferentially to inhibit IgE production by IL-4-treated human B cells. It is shown here that rapamycin inhibits both activation of the human germ line epsilon promoter by IL-4 and IL-4-inducible phosphorylation of HMG-I(Y). These findings demonstrate a rapamycin-sensitive pathway that transduces signals from the IL-4 receptor to nuclear factors that regulate inducible transcription. The affinity of normal nuclear HMG-I(Y) for DNA is increased by dephosphorylation in vitro, whereas in vitro kinase reactions using casein kinase II decrease recombinant HMG-I(Y) binding to DNA. These data further suggest a novel mechanism in which phosphorylation triggered by IL-4 or other cytokines could regulate the effects of HMG-I(Y) on gene transcription.

MeSH Terms (31)

Amino Acid Sequence Animals B-Lymphocytes Base Sequence Casein Kinase II Cell Line Cell Nucleus Consensus Sequence DNA-Binding Proteins High Mobility Group Proteins HMGA1a Protein Humans Immunosuppressive Agents Interleukin-4 Mice Molecular Sequence Data Oligodeoxyribonucleotides Peptide Fragments Peptide Mapping Phosphates Phosphopeptides Phosphorylation Polyenes Promoter Regions, Genetic Protein-Serine-Threonine Kinases Recombinant Proteins Sequence Homology, Amino Acid Signal Transduction Sirolimus Transfection Trypsin

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