       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).

