Document Detail


IL-4-induced gene-1 is a leukocyte L-amino acid oxidase with an unusual acidic pH preference and lysosomal localization.
MedLine Citation:
PMID:  15383589     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
IL-4-induced gene-1 (Il4i1 or Fig1) initially isolated as a gene of unknown function from mouse B lymphocytes, is limited in expression to primarily immune tissues and genetically maps to a region of susceptibility to autoimmune disease. The predicted Il4i1 protein (IL4I1) sequence is most similar to apoptosis-inducing protein and Apoxin I, both l-amino acid oxidases (LAAO; Enzyme Commission 1.4.3.2). We demonstrate that IL4I1 has unique LAAO properties. IL4I1 has preference for aromatic amino acid substrates, having highest specific activity with phenylalanine. In support of this selectivity, IL4I1 is inhibited by aromatic competitors (benzoic acid and para-aminobenzoic acid), but not by nonaromatic LAAO inhibitors. Il4i1 protein and enzyme activity is found in the insoluble fraction of transient transfections, implying an association with cell membrane and possibly intracellular organelles. Indeed, IL4I1 has the unique property of being most active at acidic pH (pH 4), suggesting it may reside preferentially in lysosomes. IL4I1 is N-linked glycosylated, a requirement for lysosomal localization. Confocal microscopy of cells expressing IL4I1 translationally fused to red fluorescent protein demonstrated that IL4I1 colocalized with GFP targeted to lysosomes and with acriflavine, a green fluorescent dye that is taken up into lysosomes. Thus, IL4I1 is a unique mammalian LAAO targeted to lysosomes, an important subcellular compartment involved in Ag processing.
Authors:
James M Mason; Mamta D Naidu; Michele Barcia; Debra Porti; Sangeeta S Chavan; Charles C Chu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  173     ISSN:  0022-1767     ISO Abbreviation:  J. Immunol.     Publication Date:  2004 Oct 
Date Detail:
Created Date:  2004-09-22     Completed Date:  2004-11-15     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4561-7     Citation Subset:  AIM; IM    
Affiliation:
Gene Therapy Vector Laboratory, North Shore-Long Island Jewish Research Institute, Department of Medicine, North Shore University Hospital and New York University School of Medicine, Manhasset, NY 11030, USA.
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MeSH Terms
Descriptor/Qualifier:
4-Aminobenzoic Acid / chemistry
Amino Acid Oxidoreductases / antagonists & inhibitors,  biosynthesis,  genetics,  metabolism*
Amino Acids, Aromatic / metabolism
Animals
Benzoic Acid / chemistry
Binding, Competitive
Enzyme Inhibitors / chemistry
Flavoproteins / antagonists & inhibitors,  biosynthesis,  genetics,  metabolism*
Hydrogen-Ion Concentration
Kinetics
L-Amino Acid Oxidase
Leukocytes / enzymology*
Lysosomes / enzymology*,  genetics
Mice
NIH 3T3 Cells
Oxidation-Reduction
Subcellular Fractions / enzymology
Substrate Specificity
Transfection
Grant Support
ID/Acronym/Agency:
AI44837/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Amino Acids, Aromatic; 0/Enzyme Inhibitors; 0/Flavoproteins; 0/Il4i1 protein, mouse; 150-13-0/4-Aminobenzoic Acid; 65-85-0/Benzoic Acid; EC 1.4.-/Amino Acid Oxidoreductases; EC 1.4.3.2/L-Amino Acid Oxidase

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