Molecular analysis of the pathophysiological binding of the platelet aggregation-inducing factor podoplanin to the C-type lectin-like receptor CLEC-2.

Molecular analysis of the pathophysiological binding of the platelet aggregation-inducing factor podoplanin to the C-type lectin-like receptor CLEC-2. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Molecular analysis of the pathophysiological binding of the platelet aggregation-inducing factor podoplanin to the C-type lectin-like receptor CLEC-2. Abstract Text:

Yukinari Kato,Mika Kato Kaneko,Akiko Kunita,Hiromi Ito,Akihiko Kameyama,Satoshi Ogasawara,Nana Matsuura,Yasushi Hasegawa,Katsue Suzuki-Inoue,Osamu Inoue,Yukio Ozaki,Hisashi Narimatsu,Yukinari Kato,Mika Kato Kaneko,Akiko Kunita,Hiromi Ito,Akihiko Kameyama,Satoshi Ogasawara,Nana Matsuura,Yasushi Hasegawa,Katsue Suzuki-Inoue,Osamu Inoue,Yukio Ozaki,Hisashi Narimatsu,

The mucin-type sialoglycoprotein podoplanin (aggrus) is involved in tumor cell-induced platelet aggregation and tumor metastasis. C-type lectin-like receptor-2 (CLEC-2) was recently identified as an endogenous receptor of podoplanin on platelets. However, the pathophysiological importance and function of CLEC-2 have not been elucidated. Here we clarified the pathophysiological interaction between podoplanin and CLEC-2 in vitro and in vivo. Using several deletion mutants of CLEC-2 expressed as Fc chimeras, we first identified an important podoplanin-recognition domain in CLEC-2. Furthermore, the podoplanin-CLEC-2 interaction was confirmed using several deletion mutants of podoplanin expressed as Fc chimeras. Not only the disialyl-core1-attached glycopeptide but also the stereostructure of the podoplanin protein was found to be critical for the CLEC-2-binding activity of podoplanin. We next synthesized various glycopeptides of podoplanin that included both the platelet aggregation-stimulating domain and O-glycan on Thr52. Interestingly, a disialyl-core1-attached glycopeptide was recognized specifically by CLEC-2. Moreover, the anti-podoplanin monoclonal antibody NZ-1 suppressed both the podoplanin-CLEC-2 interaction and podoplanin-induced pulmonary metastasis, suggesting that CLEC-2 is the first pathophysiological receptor of podoplanin to be identified. In summary, we clarified the molecular interaction in vitro and in vivo between a platelet aggregation-inducing factor, podoplanin, and its specific pathophysiological receptor on platelets, CLEC-2. Podoplanin and CLEC-2 might represent promising therapeutic targets in cancer metastasis.

Molecular analysis of the pathophysiological binding of the platelet aggregation-inducing factor podoplanin to the C-type lectin-like receptor CLEC-2. Publishing Authors By Initials

Y Kato,MK Kaneko,A Kunita,H Ito,A Kameyama,S Ogasawara,N Matsuura,Y Hasegawa,K Suzuki-Inoue,O Inoue,Y Ozaki,H Narimatsu,Y Kato,MK Kaneko,A Kunita,H Ito,A Kameyama,S Ogasawara,N Matsuura,Y Hasegawa,K Suzuki-Inoue,O Inoue,Y Ozaki,H Narimatsu,

For similar abstracts research abstracts see: abstracts research

PUBMED ID PMID:

MEDLINE DATE:

Molecular analysis of the pathophysiological binding of the platelet aggregation-inducing factor podoplanin to the C-type lectin-like receptor CLEC-2. Journal Published:

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

Journal: Cancer science

VOLUME: 99

Page Numbers: 54-61

Journal Abbreviation: Cancer Sci.

ISSN: 1349-7006

DAY: 18

MONTH: 10

YEAR: 2007

Molecular analysis of the pathophysiological binding of the platelet aggregation-inducing factor podoplanin to the C-type lectin-like receptor CLEC-2. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 101168776

Molecular analysis of the pathophysiological binding of the platelet aggregation-inducing factor podoplanin to the C-type lectin-like receptor CLEC-2. Keywords Mesh Terms:

KEYWORDS:

MESH TERMS:

Chemical & Substance for Abstract: Molecular analysis of the pathophysiological binding of the platelet aggregation-inducing factor podoplanin to the C-type lectin-like receptor CLEC-2. Information

Substance Name:

Registry Number:

Grant and Affiliation Information for Molecular analysis of the pathophysiological binding of the platelet aggregation-inducing factor podoplanin to the C-type lectin-like receptor CLEC-2.

AFFILIATION: Research Center for Medical Glycoscience, National Institute of Advanced Industrial Science and Technology, Open Space Laboratory C-2, 1-1-1 Umezono, Tsukuba, Ibaraki 305-8568, Japan.

Country: England

AGENCY:

GRANT:

ACRONYM:

MEDLINETA: Cancer Sci

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Molecular analysis of the pathophysiological binding of the platelet aggregation-inducing factor podoplanin to the C-type lectin-like receptor CLEC-2 Related Publications

• A caffeine-sensitive membrane electrode: previous misleading report and present approach.
• Accumulation of free complex-type N-glycans in MKN7 and MKN45 stomach cancer cells.
• Alpha (1,3/1,4)fucosyltransferase (FucT-III) gene is inactivated by a single amino acid substitution in Lewis histo-blood type negative individuals.
• Assignment of the human alpha 1,3-fucosyltransferase IX gene (FUT9) to chromosome band 6q16 by in situ hybridization.
• Cloning and characterization of a novel UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase, pp-GalNAc-T14.
• Cloning and sequencing of a full-length cDNA of mouse N-acetylglucosamine (beta 1-4)galactosyltransferase.
• Engineering of mucin-type human glycoproteins in yeast cells.
• Functional characterization of human and cynomolgus monkey cytochrome P450 2E1 enzymes.
• Genetic and enzymatic evidence for Lewis enzyme expression in Lewis-negative cancer patients.
• Human alpha-1,3 fucosyltransferase (FucT-VI) gene is located at only 13 kb 3' to the Lewis type fucosyltransferase (FucT-III) gene on chromosome 19.
• Increased expression of highly sulfated keratan sulfate synthesized in malignant astrocytic tumors.
• Influence of CYP2C19*18 and CYP2C19*19 alleles on omeprazole 5-hydroxylation: in vitro functional analysis of recombinant enzymes expressed in Saccharomyces cerevisiae.
• Interaction of bisphenol a with human UDP-glucuronosyltransferase 1A6 enzyme.
• Molecular analysis of the pathophysiological binding of the platelet aggregation-inducing factor podoplanin to the C-type lectin-like receptor CLEC-2.
• Molecular behavior of mutant Lewis enzymes in vivo.
• Murine monoclonal antibody recognizing human alpha(1,3/1,4)fucosyltransferase.
• Polylactosamine on glycoproteins influences basal levels of lymphocyte and macrophage activation.
• The aberrant expression of Lewis a antigen in intestinal metaplastic cells of gastric mucosa is caused by augmentation of Lewis enzyme expression.
• Up-regulation of Lewis enzyme (Fuc-TIII) and plasma-type alpha1,3fucosyltransferase (Fuc-TVI) expression determines the augmented expression of sialyl Lewis x antigen in non-small cell lung cancer.