Characterization of the human beta -glucan receptor and its alternatively spliced isoforms

J A Willment, S Gordon, G D Brown

Research output: Contribution to journalArticle

241 Citations (Scopus)

Abstract

beta-1,3-d-Glucans are biological response modifiers with potent effects on the immune system. A number of receptors are thought to play a role in mediating these responses, including murine Dectin-1, which we recently identified as a beta-glucan receptor. In this study we describe the characterization of the human homologue of this receptor and show that it is structurally and functionally similar to the mouse receptor. The human beta-glucan receptor is a type II transmembrane receptor with a single extracellular carbohydrate recognition domain and an immunoreceptor tyrosine activation motif in its cytoplasmic tail. The human beta-glucan receptor is widely expressed and functions as a pattern recognition receptor, recognizing a variety of beta-1,3- and/or beta-1,6-linked glucans as well as intact yeast. In contrast to the murine receptor, the human receptor mRNA is alternatively spliced, resulting in two major (A and B) and six minor isoforms. The two major isoforms differ by the presence of a stalk region separating the carbohydrate recognition domain from the transmembrane region and are the only isoforms that are functional for beta-glucan binding. The human receptor also binds T-lymphocytes at a site distinct from the beta-glucan binding site, indicating that this receptor can recognize both endogenous and exogenous ligands.
Original languageEnglish
Pages (from-to)43818-23
Number of pages6
JournalThe Journal of Biological Chemistry
Volume276
Issue number47
DOIs
Publication statusPublished - 2001

Fingerprint

Protein Isoforms
beta-Glucans
Glucans
Carbohydrates
Pattern Recognition Receptors
T-cells
Immune system
Immunologic Factors
Yeast
Tyrosine
Chemical activation
Binding Sites
Ligands
Messenger RNA
Tail
Immune System
Yeasts
beta-glucan receptor
T-Lymphocytes
dectin 1

Keywords

  • Alternative Splicing
  • Animals
  • Base Sequence
  • Candida
  • Cell Line
  • Cloning, Molecular
  • DNA Primers
  • Humans
  • Mice
  • Molecular Sequence Data
  • Protein Binding
  • Receptors, Immunologic
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes

Cite this

Characterization of the human beta -glucan receptor and its alternatively spliced isoforms. / Willment, J A; Gordon, S; Brown, G D.

In: The Journal of Biological Chemistry, Vol. 276, No. 47, 2001, p. 43818-23.

Research output: Contribution to journalArticle

@article{d1a9706e2c124062b58e018617b2a742,
title = "Characterization of the human beta -glucan receptor and its alternatively spliced isoforms",
abstract = "beta-1,3-d-Glucans are biological response modifiers with potent effects on the immune system. A number of receptors are thought to play a role in mediating these responses, including murine Dectin-1, which we recently identified as a beta-glucan receptor. In this study we describe the characterization of the human homologue of this receptor and show that it is structurally and functionally similar to the mouse receptor. The human beta-glucan receptor is a type II transmembrane receptor with a single extracellular carbohydrate recognition domain and an immunoreceptor tyrosine activation motif in its cytoplasmic tail. The human beta-glucan receptor is widely expressed and functions as a pattern recognition receptor, recognizing a variety of beta-1,3- and/or beta-1,6-linked glucans as well as intact yeast. In contrast to the murine receptor, the human receptor mRNA is alternatively spliced, resulting in two major (A and B) and six minor isoforms. The two major isoforms differ by the presence of a stalk region separating the carbohydrate recognition domain from the transmembrane region and are the only isoforms that are functional for beta-glucan binding. The human receptor also binds T-lymphocytes at a site distinct from the beta-glucan binding site, indicating that this receptor can recognize both endogenous and exogenous ligands.",
keywords = "Alternative Splicing, Animals, Base Sequence, Candida, Cell Line, Cloning, Molecular, DNA Primers, Humans, Mice, Molecular Sequence Data, Protein Binding, Receptors, Immunologic, Reverse Transcriptase Polymerase Chain Reaction, T-Lymphocytes",
author = "Willment, {J A} and S Gordon and Brown, {G D}",
year = "2001",
doi = "10.1074/jbc.M107715200",
language = "English",
volume = "276",
pages = "43818--23",
journal = "The Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC",
number = "47",

}

TY - JOUR

T1 - Characterization of the human beta -glucan receptor and its alternatively spliced isoforms

AU - Willment, J A

AU - Gordon, S

AU - Brown, G D

PY - 2001

Y1 - 2001

N2 - beta-1,3-d-Glucans are biological response modifiers with potent effects on the immune system. A number of receptors are thought to play a role in mediating these responses, including murine Dectin-1, which we recently identified as a beta-glucan receptor. In this study we describe the characterization of the human homologue of this receptor and show that it is structurally and functionally similar to the mouse receptor. The human beta-glucan receptor is a type II transmembrane receptor with a single extracellular carbohydrate recognition domain and an immunoreceptor tyrosine activation motif in its cytoplasmic tail. The human beta-glucan receptor is widely expressed and functions as a pattern recognition receptor, recognizing a variety of beta-1,3- and/or beta-1,6-linked glucans as well as intact yeast. In contrast to the murine receptor, the human receptor mRNA is alternatively spliced, resulting in two major (A and B) and six minor isoforms. The two major isoforms differ by the presence of a stalk region separating the carbohydrate recognition domain from the transmembrane region and are the only isoforms that are functional for beta-glucan binding. The human receptor also binds T-lymphocytes at a site distinct from the beta-glucan binding site, indicating that this receptor can recognize both endogenous and exogenous ligands.

AB - beta-1,3-d-Glucans are biological response modifiers with potent effects on the immune system. A number of receptors are thought to play a role in mediating these responses, including murine Dectin-1, which we recently identified as a beta-glucan receptor. In this study we describe the characterization of the human homologue of this receptor and show that it is structurally and functionally similar to the mouse receptor. The human beta-glucan receptor is a type II transmembrane receptor with a single extracellular carbohydrate recognition domain and an immunoreceptor tyrosine activation motif in its cytoplasmic tail. The human beta-glucan receptor is widely expressed and functions as a pattern recognition receptor, recognizing a variety of beta-1,3- and/or beta-1,6-linked glucans as well as intact yeast. In contrast to the murine receptor, the human receptor mRNA is alternatively spliced, resulting in two major (A and B) and six minor isoforms. The two major isoforms differ by the presence of a stalk region separating the carbohydrate recognition domain from the transmembrane region and are the only isoforms that are functional for beta-glucan binding. The human receptor also binds T-lymphocytes at a site distinct from the beta-glucan binding site, indicating that this receptor can recognize both endogenous and exogenous ligands.

KW - Alternative Splicing

KW - Animals

KW - Base Sequence

KW - Candida

KW - Cell Line

KW - Cloning, Molecular

KW - DNA Primers

KW - Humans

KW - Mice

KW - Molecular Sequence Data

KW - Protein Binding

KW - Receptors, Immunologic

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - T-Lymphocytes

U2 - 10.1074/jbc.M107715200

DO - 10.1074/jbc.M107715200

M3 - Article

VL - 276

SP - 43818

EP - 43823

JO - The Journal of Biological Chemistry

JF - The Journal of Biological Chemistry

SN - 0021-9258

IS - 47

ER -