Different CD40-mediated signaling events require distinct CD40 structural features

Bruce S Hostager; Yina Hsing; Dan E Harms; Gail A Bishop

doi:10.4049/jimmunol.157.3.1047

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Different CD40-mediated signaling events require distinct CD40 structural features

Journal article

Peer reviewed

Different CD40-mediated signaling events require distinct CD40 structural features

Bruce S Hostager, Yina Hsing, Dan E Harms and Gail A Bishop

The Journal of immunology (1950), Vol.157(3), pp.1047-1053

08/01/1996

DOI: 10.4049/jimmunol.157.3.1047

PMID: 8757608

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Abstract

Signals delivered to B cells through CD40 are critical to the development of humoral immune responses. In this study we characterize regions of the 62-amino acid cytoplasmic domain of human CD40 (hCD40) that are essential for signal transduction and examine the functional consequences of mutations in these regions. A panel of mutant hCD40 molecules was stably expressed in mouse B cell lines and tested for its ability to stimulate Ab secretion, homotypic adhesion, and increased surface expression of B7, Fas, CD23, LFA-1, and intracellular adhesion molecule-1. Our results indicate that CD40 contains at least two major signaling determinants in the cytoplasmic domain: one disrupted by a truncation of 22 amino acids, and a second disrupted by the removal of 10 additional amino acids. The second determinant includes threonine 234, a residue previously shown to be important in CD40 signal transduction. Our functional analysis of alanine and serine substitutions at position 234 indicates that phosphorylation of this residue may be important for full CD40 signaling activity.

Flow Cytometry

Amino Acid Sequence

CD40 Antigens - physiology

Cell Line

Cricetinae

Mutagenesis, Site-Directed

Humans

Molecular Sequence Data

Intercellular Adhesion Molecule-1

Lymphocyte Function-Associated Antigen-1 - metabolism

Structure-Activity Relationship

fas Receptor - metabolism

Cell Adhesion

Immunoglobulin M - metabolism

CD40 Antigens - chemistry

Animals

Receptors, IgE - metabolism

Antibody Formation

Cell Aggregation

Signal Transduction - physiology

CD40 Antigens - genetics

Mice

Details

Title: Subtitle: Different CD40-mediated signaling events require distinct CD40 structural features
Creators: Bruce S Hostager - Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA
Yina Hsing
Dan E Harms
Gail A Bishop
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.157(3), pp.1047-1053
DOI: 10.4049/jimmunol.157.3.1047
PMID: 8757608
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Publisher: United States
Grant note: AI28847 / NIAID NIH HHS T32 AI07485 / NIAID NIH HHS T32 AI07260 / NIAID NIH HHS
Language: English
Date published: 08/01/1996
Academic Unit: Microbiology and Immunology; President
Record Identifier: 9984001153602771

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