ROLE OF ADF/THIOREDOXIN IN SIGNAL TRANSDUCTION MECHANISMS: INVOLVEMENT IN CELLULAR PROLIFERATION (MEETING ABSTRACT)

Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.

ROLE OF ADF/THIOREDOXIN IN SIGNAL TRANSDUCTION MECHANISMS: INVOLVEMENT IN CELLULAR PROLIFERATION (MEETING ABSTRACT)

Proc Annu Meet Am Assoc Cancer Res; 33:A2090 1992. Unique Identifier : AIDSLINE ICDB/92684627
Biguet C; Wakasugi N; Wakasugi H; Tursz T; Laboratoire de Biologie des Tumeurs Humaines, URA 1156 CNRS,; Institut Gustave Roussy, 94805 Villejuif, France

Abstract: We have shown that ADF (adult T-cell leukemia [ATL]-derived factor) is produced and released at high levels by both HTLV-I-infected ATL cells and EBV-immortalized B lymphocytes. ADF is the human equivalent of the disulfide-reducing enzyme thioredoxin (TRX). Recombinant ADF alone or in synergy with other cytokines, such as IL-1, IL-2, IL-4 and IL-6, was able to promote the growth of 3B6 cells. We have investigated the effect of ADF/TRX on second-messenger signal transduction pathways using the EBV-containing lymphoblastoid cell line 1G8, a low producer of ADF and the E coli TRX system. These 1G8 cells responded to the reduced form of TRX (TRX[SH]2) by proliferating, and this response was blocked by staurosporine, a protein kinase C (PKC) inhibitor. Analysis of the signaling pathway showed that TRX(SH)2 stimulated the rapid hydrolysis of inositol-biphosphate to yield diacylglycerol and inositol 1,4,5-triphosphate. The TRX(SH)2 also induced an increase in intracellular Ca++ concentration, which comes not only from extracellular culture medium but also from intracellular stores. After TRX(SH)2 stimulation, the translocation of the PKC to the membrane was observed. These results suggested that ADF/TRX-induced cellular growth involved a signal transduction pathway which involves PKC activation. The data emphasized the role of ADF/TRX in the autocrine growth of EBV- or HTLV-I-infected lymphocytes.

Keywords: Alkaloids/PHARMACOLOGY B-Lymphocytes/MICROBIOLOGY Cell Division/*DRUG EFFECTS Cell Transformation, Viral Enzyme Activation Herpesvirus 4, Human Human HTLV-I Neoplasm Proteins/*PHYSIOLOGY Protein Kinase C/ANTAGONISTS & INHIB/METABOLISM Recombinant Proteins/PHYSIOLOGY Second Messenger Systems *Signal Transduction Thioredoxin/*ANALYSIS Tumor Cells, Cultured ABSTRACT
921230
M92C5373

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