A role for the epidermal growth factor-like domain of P-selectin in ligand recognition and cell adhesion.
The selectin family of adhesion molecules mediates the initial interactions of leukocytes with endothelium. The extracellular region of each selectin contains an amino-terminal C-type lectin domain, followed by an EGF-like domain and multiple short consensus repeat units (SCR). Previous studies have indirectly suggested a role for each of the extracellular domains of the selectins in cell adhesion. In this study, a panel of chimeric selectins created by exchange of domains between L- and P-selectin was used to directly examine the role of the extracellular domains in cell adhesion. Exchange of only the lectin domains between L- and P-selectin conferred the adhesive and ligand recognition functions of the lectin domain of the parent molecule. However, chimeric selectins which contained both the lectin domain of L-selectin and the EGF-like domain of P-selectin exhibited dual ligand-binding specificity. These chimeric proteins supported adhesion both to myeloid cells and to high endothelial venules (HEV) of lymph nodes and mesenteric venules in vivo. Exchange of the SCR domains had no detectable effect on receptor function or specificity. Thus, the EGF-like domain of P-selectin may play a direct role in ligand recognition and leukocyte adhesion mediated by P-selectin, with the lectin plus EGF-like domains collectively forming a functional ligand recognition unit.
Kansas
G S
GS
Division of Tumor Immunology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
Saunders
K B
KB
Ley
K
K
Zakrzewicz
A
A
Gibson
R M
RM
Furie
B C
BC
Furie
B
B
Tedder
T F
TF
D000818:Animals; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000378:metabolism; D002460:Cell Line; D003001:Cloning, Molecular; D004815:Epidermal Growth Factor / Q000378:metabolism*; D006801:Humans; D019041:L-Selectin; D008024:Ligands; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D051381:Rats; D014407:Tumor Cells, Cultured
D015815:Cell Adhesion Molecules; D008024:Ligands; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; D019041:L-Selectin; D004815:Epidermal Growth Factor