Regulation of CTL by ecto-nictinamide adenine dinucleotide (NAD) involves ADP-ribosylation of a p56lck-associated protein.

Important note: Information in this article was accurate in 1996. The state of the art may have changed since the publication date.

Regulation of CTL by ecto-nictinamide adenine dinucleotide (NAD) involves ADP-ribosylation of a p56lck-associated protein.

J Immunol. 1996 Apr 15;156(8):2819-27. Unique Identifier : AIDSLINE MED/96183236
Wang J; Nemoto E; Dennert G; Department of Molecular Immunology, University of Southern; California School of Medicine, Los Angeles 90033, USA.

Abstract: Receptor-mediated activation of T lymphocytes involves protein phosphorylation by several protein tyrosine kinases, among those the src-related enzymes p56lck and p59fyn. Accumulating evidence supports the notion that these enzymes are regulated by tyrosine phosphorylation and dephosphorylation, but much is yet to be learned about regulation of their activity. Here we demonstrate that p56lck but not p59fyn exists as a complex with a 40-kDa protein, which in its ADP-ribosylated form inhibits p56lck kinase activity. ADP-ribosylation of this protein is mediated by an arginine-specific mono-ADP-ribosyltransferase, which makes use of extracellular nicotinamide adenine dinucleotide (NAD). This enzyme is a glycosyl-phosphatidylinositol-anchored protein releasable from the surface of cytotoxic T cells by glycosyl-phosphatidylinositol-specific phospholipase C. Release of arginine-specific mono-ADP-ribosyltransferase results in failure of extracellular NAD to downmodulate p56lck kinase activity. Concomitant to suppression of the kinase by NAD, CD8 mediated transmembrane signaling and p56lck kinase activation are inhibited.

Keywords: src-Family Kinases/ANTAGONISTS & INHIB/*METABOLISM Adenosine Diphosphate Ribose/*METABOLISM Animal Cytotoxicity, Immunologic/*DRUG EFFECTS CD8-Positive T-Lymphocytes/IMMUNOLOGY Down-Regulation (Physiology)/DRUG EFFECTS/IMMUNOLOGY Mice Mice, Inbred BALB C Mice, Inbred C57BL Molecular Weight NAD/*PHARMACOLOGY NAD+ ADP-Ribosyltransferase/METABOLISM Proto-Oncogene Proteins/METABOLISM Receptors, Antigen, T-Cell/DRUG EFFECTS/PHYSIOLOGY Signal Transduction/DRUG EFFECTS Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. T-Lymphocytes, Cytotoxic/*DRUG EFFECTS/ENZYMOLOGY/*METABOLISM JOURNAL ARTICLE
960830
M9681183

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