A sulfated proteoglycan as a novel ligand for CD44.
We have identified a novel ligand for CD44, a cell surface glycoprotein implicated in tumor metastasis and lymphocyte homing. When the mouse T cell line CTLL-2 was transfected with cDNA encoding a hemopoietic form of mouse CD44, CTLL-2 cells exhibited a new self-adhesive phenotype, forming large aggregates. The aggregation was blocked by neutralizing anti CD44 monoclonal antibody but unaffected by hyaluronidase, indicating the involvement of CD44 and its non-hyaluronate ligand in the cell aggregation. The ability to induce CD44-dependent aggregation was found in culture supernatants of CTLL-2 and its CD44 transfectants. The use of CD44-immunoglobulin chimeric protein revealed that CTLL-2 and its transfectants synthesized a large-molecular weight protein (gp600) which bound specifically to CD44. The gp600 was readily labeled with radioactive sulfate, and treatment of gp600 with chondroitinase ABC or ACII generated a lower molecular weight species (18-22 kDa), suggesting that gp600 consists of a small core protein with chondroitin sulfate glycosaminoglycan side chains. However, binding of CD44 to glycosaminoglycans such as chondroitin 4-sulfate, chondroitin 6-sulfate, and dermatan sulfate was undetectable, suggesting either that a novel chondroitin-type glycosaminoglycan is recognized by CD44 or that a particular configuration of the glycosaminoglycan 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 / Q000737:chemistry / Q000378:metabolism*; D002449:Cell Aggregation / Q000502:physiology; D002478:Cells, Cultured; D002809:Chondroitin Sulfates; D018960:Hyaluronan Receptors; D051379:Mice; D011233:Precipitin Tests; D011509:Proteoglycans / Q000737:chemistry / Q000378:metabolism*; D011869:Radioligand Assay; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism*; D016201:Receptors, Lymphocyte Homing / Q000737:chemistry / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism / Q000502:physiology*; D014162:Transfection; D033921:Vesicular Transport Proteins
D002352:Carrier Proteins; D018960:Hyaluronan Receptors; D011509:Proteoglycans; D011956:Receptors, Cell Surface; D016201:Receptors, Lymphocyte Homing; D033921:Vesicular Transport Proteins; C075430:serglycin; D002809:Chondroitin Sulfates