CD44 binds a chondroitin sulfate proteoglycan, aggrecan.
Here we report that CD44 binds a chondroitin sulfate (CS) proteoglycan, aggrecan, a major component of cartilage. Soluble CD44-IgG and CD44(+) cells bound to aggrecan from rat chondrosarcoma and bovine cartilage, immobilized on microtiter plates. In both cases, binding was blocked by a neutralizing anti-CD44 mAb or by the pretreatment of aggrecan with chondroitinase, but not hyaluronidase or keratanase, indicating that CD44 binds aggrecan in a manner dependent on CS side chains of aggrecan and that hyaluronic acid is not involved in the binding. Structural analysis showed that glycosaminoglycans of aggrecan from rat chondrosarcoma and bovine articular cartilage consist of mainly CS A and a mixture of CS A and C respectively. When immobilized on microtiter plates, both CS A and C bound CD44-IgG, and the reaction was specifically inhibited by an anti-CD44 mAb. In addition, aggrecan augmented apoptosis in cells expressing CD44-Fas chimeric molecules in synergy with a non-blocking anti-CD44 mAb IRAWB14.4, suggesting that CD44-aggrecan interaction can induce oligomerization of the chimeric molecules. These results suggest that aggrecan interacts with CD44 to mediate cell adhesion and to trigger oligomerization of CD44 molecules, which may lead to intracellular signaling.
Department of Bioregulation, Biomedical Research Center, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita 565-0871, Japan.
T
T
Fujimoto
H
H
Kawashima
T
T
Tanaka
M
M
Hirose
N
N
Toyama-Sorimachi
Y
Y
Matsuzawa
M
M
Miyasaka
D053674:Aggrecans; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D017209:Apoptosis; D019921:Biotinylation; D002358:Cartilage, Articular / Q000737:chemistry; D002417:Cattle; D002645:Chickens; D019765:Chondroitin ABC Lyase / Q000494:pharmacology; D002809:Chondroitin Sulfates / Q000032:analysis; D002813:Chondrosarcoma / Q000737:chemistry / Q000473:pathology; D016895:Culture Media, Serum-Free; D004187:Disaccharides / Q000032:analysis; D016326:Extracellular Matrix Proteins; D018960:Hyaluronan Receptors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000494:pharmacology; D006821:Hyaluronoglucosaminidase / Q000494:pharmacology; D037181:Lectins, C-Type; D008297:Male; D051379:Mice; D008806:Mice, Inbred AKR; D011485:Protein Binding / Q000187:drug effects; D011509:Proteoglycans / Q000378:metabolism*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000502:physiology; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000235:genetics / Q000502:physiology
C508320:Acan protein, mouse; C508321:Acan protein, rat; D053674:Aggrecans; D000911:Antibodies, Monoclonal; D016895:Culture Media, Serum-Free; D004187:Disaccharides; D016326:Extracellular Matrix Proteins; D018960:Hyaluronan Receptors; D037181:Lectins, C-Type; D011509:Proteoglycans; D011993:Recombinant Fusion Proteins; D019014:fas Receptor; D006820:Hyaluronic Acid; D002809:Chondroitin Sulfates; D006821:Hyaluronoglucosaminidase; D019765:Chondroitin ABC Lyase