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1996-03-09
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Document 0434
DOCN M9650434
TI Signal transduction pathway of interleukin-4 and interleukin-13 in human
B cells derived from X-linked severe combined immunodeficiency patients.
DT 9605
AU Izuhara K; Heike T; Otsuka T; Yamaoka K; Mayumi M; Imamura T; Niho Y;
Harada N; Department of Human Genetics, National Institute of Genetics,;
Shizuoka, Japan.
SO J Biol Chem. 1996 Jan 12;271(2):619-22. Unique Identifier : AIDSLINE
MED/96132783
AB Interleukin-4 (IL-4) and IL-13 are functionally similar cytokines. The
functional IL-4 receptor (IL-4R) consists of the IL-4R alpha chain
(IL-4R alpha) and the IL-2R gamma chain (gamma c), which is shared by
the IL-2, IL-7, IL-9, and IL-15 receptors. The functional IL-13R is
thought to involve the IL-4R alpha but not gamma c. In this study, we
have analyzed activation of members of the Janus tyrosine kinase (Jak)
family and signal transducers and activators of transcription (STAT) 6
induced by IL-4 and IL-13 in Epstein-Barr virus-transformed B cells
derived from two patients of X-linked severe combined immunodeficiency,
who have mutations of the gamma c gene in the extracellular and
intracellular domains. In these B cells, IL-4 failed to induce tyrosine
phosphorylation of Jak3 and activation of STAT6, or activation of these
molecules was significantly decreased compared with Epstein-Barr
virus-transformed normal B cells. In contrast, IL-13 activated STAT6 in
these cells as well as normal B cells. However, Jak3 was not activated
by IL-13, even in normal B cells. These results clearly indicated that
gamma c is essential for activation of Jak3 and STAT6 in the signal
transduction pathway of IL-4 in human B cells and that IL-13 does not
utilize gamma c but activates STAT6 through an alternative pathway,
which is not impaired in B cells of X-linked severe combined
immunodeficiency patients.
DE B-Lymphocytes/*METABOLISM Base Sequence Cells, Cultured Human
Interleukin-13/*METABOLISM/PHARMACOLOGY
Interleukin-4/*METABOLISM/PHARMACOLOGY Molecular Sequence Data Severe
Combined Immunodeficiency/IMMUNOLOGY/*METABOLISM Signal Transduction
Support, Non-U.S. Gov't JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).