Activation of human endothelial cells via S-endo-1 antigen (CD146) stimulates the tyrosine phosphorylation of focal adhesion kinase p125(FAK).
S-Endo-1 antigen (CD146), a transmembrane receptor also known as MUC18/MCAM, is a member of the immunoglobulin superfamily and belongs to a group of cell adhesion molecules. CD146 is highly expressed on the whole vascular tree. We demonstrate here that engagement of CD146 on human endothelial cells isolated from cord blood results in tyrosine phosphorylation of a large panel of cellular proteins, although no tyrosine phosphorylation of CD146 was detected. In particular, CD146 cross-linking induces the tyrosine phosphorylation of the protein tyrosine kinase p125(FAK) as well as p125(FAK) association with paxillin, both events being inhibited by cytochalasin D. No direct association of CD146 with p125(FAK) was observed. Consistent with these data, CD146 associates with p59(fyn), a Src family kinase known to phosphorylate p125(FAK). The identification of a signaling pathway initiated by CD146 engagement and which includes p59(fyn), p125(FAK), and paxillin indicates that CD146 participates in outside-in signaling in endothelial cells.
Laboratoire d'Hématologie-Immunologie, Unité de Formation et de Recherche Pharmacie, 13385 Marseille, France.
F
F
Anfosso
N
N
Bardin
V
V
Francès
E
E
Vivier
L
L
Camoin-Jau
J
J
Sampol
F
F
Dignat-George
D015703:Antigens, CD; D000954:Antigens, Surface / Q000378:metabolism*; D051929:CD146 Antigen; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D008562:Membrane Glycoproteins; D019006:Neural Cell Adhesion Molecules; D051419:Paxillin; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051076:Proto-Oncogene Proteins c-fyn; D014443:Tyrosine / Q000378:metabolism*
D015703:Antigens, CD; D000954:Antigens, Surface; D051929:CD146 Antigen; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; C497902:MCAM protein, human; D008562:Membrane Glycoproteins; D019006:Neural Cell Adhesion Molecules; C496061:PXN protein, human; D051419:Paxillin; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; C494957:FYN protein, human; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; D051076:Proto-Oncogene Proteins c-fyn