Functional significance of Asn-linked glycosylation of proteinase 3 for enzymatic activity, processing, targeting, and recognition by anti-neutrophil cytoplasmic antibodies.

Functional significance of Asn-linked glycosylation of proteinase 3 for enzymatic activity, processing, targeting, and recognition by anti-neutrophil cytoplasmic antibodies. Research Abstract Details 

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Functional significance of Asn-linked glycosylation of proteinase 3 for enzymatic activity, processing, targeting, and recognition by anti-neutrophil cytoplasmic antibodies. Abstract Text:

Ulrich Specks,David N Fass,Javier D Finkielman,Amber M Hummel,Margaret A Viss,Robert D Litwiller,Cari J McDonald,Ulrich Specks,David N Fass,Javier D Finkielman,Amber M Hummel,Margaret A Viss,Robert D Litwiller,Cari J McDonald,

Proteinase 3 (PR3) is a neutral serine protease stored in neutrophil granules. It has substantial sequence homology with elastase, cathepsin G and azurocidin. PR3 is the target antigen for autoantibodies (ANCA) in Wegener's granulomatosis, a necrotizing vasculitis syndrome. ANCA have been implicated in the pathogenesis of this disease. PR3 has two potential Asn-linked glycosylation sites. This study was designed to determine the occupancy of these glycosylation sites, and to evaluate their effect on enzymatic function, intracellular processing, targeting to granules and recognition by ANCA. We found that glycosylation occurs at both sites in native neutrophil PR3 and in wild type recombinant PR3 (rPR3) expressed in HMC-1 cells. Using glycosylation deficient rPR3 mutants we found that glycosylation at Asn-147, but not at Asn-102, is critical for thermal stability, and for optimal hydrolytic activity of PR3. Efficient amino-terminal proteolytic processing of rPR3 is dependent on glycosylation at Asn-102. Targeting to granules is not dependent on glycosylation, but unglycosylated rPR3 gets secreted preferentially into media supernatants. Finally, a capture ELISA for ANCA detection, using rPR3 glycosylation variants as target antigens, reveals that in about 20% of patients, epitope recognition by ANCA is affected by the glycosylation status of PR3.

Functional significance of Asn-linked glycosylation of proteinase 3 for enzymatic activity, processing, targeting, and recognition by anti-neutrophil cytoplasmic antibodies. Publishing Authors By Initials

U Specks,DN Fass,JD Finkielman,AM Hummel,MA Viss,RD Litwiller,CJ McDonald,U Specks,DN Fass,JD Finkielman,AM Hummel,MA Viss,RD Litwiller,CJ McDonald,

For similar biochemical phenomena, metabolism, and nutrition: metabolism: biological transport: protein transport research abstracts see: biochemical phenomena, metabolism, and nutrition: metabolism: biological transport: protein transport research

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Functional significance of Asn-linked glycosylation of proteinase 3 for enzymatic activity, processing, targeting, and recognition by anti-neutrophil cytoplasmic antibodies. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of biochemistry

VOLUME: 141

Page Numbers: 101-12

Journal Abbreviation: J. Biochem.

ISSN: 0021-924X

DAY: 11

MONTH: 12

YEAR: 2006

Functional significance of Asn-linked glycosylation of proteinase 3 for enzymatic activity, processing, targeting, and recognition by anti-neutrophil cytoplasmic antibodies. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 376600

Functional significance of Asn-linked glycosylation of proteinase 3 for enzymatic activity, processing, targeting, and recognition by anti-neutrophil cytoplasmic antibodies. Keywords Mesh Terms:

KEYWORDS: Protein Transport

MESH TERMS: physiology

Chemical & Substance for Abstract: Functional significance of Asn-linked glycosylation of proteinase 3 for enzymatic activity, processing, targeting, and recognition by anti-neutrophil cytoplasmic antibodies. Information

Substance Name: Myeloblastin

Registry Number: EC 3.4.21.76

Grant and Affiliation Information for Functional significance of Asn-linked glycosylation of proteinase 3 for enzymatic activity, processing, targeting, and recognition by anti-neutrophil cytoplasmic antibodies.

AFFILIATION: Thoracic Disease Research Unit, Mayo Clinic and Foundation, Rochester, MN 55905, USA. specks.ulrich@mayo.edu

Country: Japan

AGENCY: United States NIAID

GRANT: R21-AI47572

ACRONYM: AI

MEDLINETA: J Biochem (Tokyo)

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