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

D. Z. Wang, P. Ray, M. Boothby

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

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 ε 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.

Original languageEnglish (US)
Pages (from-to)22924-22932
Number of pages9
JournalJournal of Biological Chemistry
Volume270
Issue number39
DOIs
StatePublished - 1995
Externally publishedYes

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Phosphorylation
Sirolimus
Interleukin-4
Transcription
Casein Kinase II
B-Lymphocytes
Non Histone Chromosomal Proteins
Chemical activation
Cells
Phosphoamino Acids
Interleukin-4 Receptors
Phosphopeptides
Lymphocytes
DNA
Immunosuppressive Agents
Germ Cells
Labeling
Serine
Immunoglobulin E
Signal Transduction

ASJC Scopus subject areas

  • Biochemistry

Cite this

Interleukin 4-inducible phosphorylation of HMG-I(Y) is inhibited by rapamycin. / Wang, D. Z.; Ray, P.; Boothby, M.

In: Journal of Biological Chemistry, Vol. 270, No. 39, 1995, p. 22924-22932.

Research output: Contribution to journalArticle

Wang, D. Z. ; Ray, P. ; Boothby, M. / Interleukin 4-inducible phosphorylation of HMG-I(Y) is inhibited by rapamycin. In: Journal of Biological Chemistry. 1995 ; Vol. 270, No. 39. pp. 22924-22932.
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