A novel ligand for CD44 is sulfated proteoglycan.
We report herein identification of a novel ligand for CD44, a cell surface glycoprotein implicated in tumor metastasis, lymphocyte differentiation and homing. A mouse T cell line CTLL-2 transfected with cDNA encoding a hemopoietic form of mouse CD44 exhibited a new self-adhesive phenotype, forming large aggregates. The aggregation was blocked by anti-CD44 mAb but little affected by hyaluronidase, indicating the involvement of CD44 and its non-hyaluronate ligand in the cell aggregation. The ability to induce CD44-dependent aggregation was observed in culture supernatants of CTLL-2 and its CD44 transfectants. Immunoprecipitation analysis using a CD44-Ig chimeric molecule indicated that CTLL-2 and its transfectants synthesized a macromolecule (gp600) which bound specifically to CD44. gp600 was readily labeled with radioactive sulfate and treatment of gp600 with chondroitinase ABC or AC II generated a lower molecular weight species (18-22 kDa), suggesting that gp600 consists of a small core protein heavily modified with chondroitin sulfate glycosaminoglycan side chains. However, when binding of CD44 was tested in vitro to chondroitinase-sensitive purified glycosaminoglycans, such as chondroitin-4-sulfate, chondroitin-6-sulfate and dermatan sulfate, no binding was demonstrable, suggesting either that a novel type of chondroitinase-sensitive glycosaminoglycan is recognized by CD44 or that association of the glycosaminoglycan with a core protein is required for recognition by CD44.
Toyama-Sorimachi
N
N
Department of Immunology, Tokyo Metropolitan Institute of Medical Science, Japan.
Miyasaka
M
M
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002449:Cell Aggregation; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D018960:Hyaluronan Receptors; D007553:Isotope Labeling; D008024:Ligands; D051379:Mice; D011233:Precipitin Tests; D011509:Proteoglycans / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism; D014162:Transfection
D002352:Carrier Proteins; D018960:Hyaluronan Receptors; D008024:Ligands; D011509:Proteoglycans; D011956:Receptors, Cell Surface; D016201:Receptors, Lymphocyte Homing; D011993:Recombinant Fusion Proteins