GM-CSF, IL-3, IL-4 and IL-5: genes and their receptors (Meeting abstract).

Important note: Information in this article was accurate in 1995. The state of the art may have changed since the publication date.

GM-CSF, IL-3, IL-4 and IL-5: genes and their receptors (Meeting abstract).

Molecular Biology of Hematopoiesis, 8th Symposium. July 9-13, 1993, Basel, Switzerland, p. 94, 1993.. Unique Identifier : AIDSLINE ICDB/95699369
Arai K; Watanabe S; Muto A; Sato N; Kinoshita T; Chen JX; Kurata H; Kosugi H; Nakagawa Y; Koyano-Nakagawa N; et al; Inst. of Medical Science, Univ. of Tokyo, Minato-ku, Tokyo, Japan

Abstract: GM-CSF induces activation of early response genes, protein tyrosine phosphorylation and proliferation of hematopoietic cells. The hGMR reconstituted by transfecting cDNAs encoding alpha and beta chains is functional in NIH3T3 cells, indicating that molecule(s) such as tyrosine kinase unique to hematopoietic cells is not essential to transduce signals. In BA/F3 pro-B cells or 3T3 cells expressing hGMR, herbimycin inhibits the induction of c-myc mRNA and cell proliferation whereas only partially inhibits the induction of c-fos/c-jun mRNAs in response to hGM-CSF. These results suggest that tyrosine kinase(s) is involved in the former but not in the latter reactions. Deletion analysis of beta chain showed that the region between amino acid positions 625 and 763 is required for activation of c-fos/c-jun genes, MAP kinase and Ras but not for the activation of c-myc gene and proliferation. These results indicate that the induction of c-fos/c-jun genes through hGM-CSFR is regulated by a pathway different from that of c-myc gene and proliferation. The structure of the genes encoding alpha chains of IL-3 and GM-CSF receptors will be also discussed. The GM-CSF promoter is composed of at least three distinct cis-acting elements (CLE0, CLEI and CLE2/GC); CLE2/GC interacts with PMA-inducible GM-kappa B (probably identical to NF-kappa B p50/p65). HTLV-I encoded Tax promotes the translocation of NF-kappa B p50/p65 from cytoplasm to nucleus and activates GM-CSF gene in the absence of antigen stimulation. CLE0 is the target for PMA and A23 187; one of the CLE0 binding factors is identical to AP1 and the other resembles NF-AT. CLE0 or NF-AT like elements in IL-3, IL-4, IL-5, GM-CSF and IL-2 promoters may account for the coordinate activation of these genes during T cell activation. Novel features of the regulation of IL-4 and IL-5 genes in TH1 and TH2 cells will be discussed.

Keywords: Animal Calcimycin/PHARMACOLOGY DNA, Complementary Granulocyte-Macrophage Colony-Stimulating Factor/*GENETICS Interleukin-3/*GENETICS Interleukin-4/*GENETICS Interleukin-5/*GENETICS Mice Phosphorylation Promoter Regions (Genetics) Quinones/PHARMACOLOGY Signal Transduction Tetradecanoylphorbol Acetate/PHARMACOLOGY Tyrosine/METABOLISM 3T3 Cells ABSTRACT
950330
M9530853

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