Activation of Human Endothelial Cells via S-Endo-1 Antigen (CD146) Stimulates the Tyrosine Phosphorylation of Focal Adhesion Kinase p125FAK

doi:10.1074/jbc.273.41.26852

Activation of Human Endothelial Cells via S-Endo-1 Antigen (CD146) Stimulates the Tyrosine Phosphorylation of Focal Adhesion Kinase p125^FAK*

From the Laboratoire d’Hématologie-Immunologie, Unitéde Formation et de Recherche Pharmacie, 13385 Marseille, and the^§Centre d’Immunologie INSERM-CNRS, Marseille Luminy and the Institut Universitaire de France, 13288 Marseille, France

Abstract

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.

Footnotes

↵* This work was supported by Grant UPRES EA 2195 from the Ministère de l’Education Nationale.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
↵‡ To whom correspondence should be addressed: Laboratoire d’Hématologie-Immunologie, UFR Pharmacie 27, Bd Jean Moulin, 13385 Marseille cedex 5, France. Tel.: 33-4-9183-5600; Fax: 33-4-9183-5602; E-mail: hematim{at}pharmacie.univ-mrs.fr.
↵2 N. Bardin, V. Francès, J. Sampol, and F. Dignat-George, manuscript in preparation.
Abbreviations:

HUVEC

human umbilical vein endothelial cell

mAb

monoclonal antibody

Tyr(P)

phosphotyrosine

anti-Tyr(P) mAb

mouse monoclonal antibody against phosphotyrosine

GAMIg

goat anti-mouse immunoglobulin

NaV

peroxovanadate

PAGE

polyacrylamide gel electrophoresis

PTK

protein tyrosine kinase

C

constant

V

variable.
- Received May 1, 1998.
- Revision received July 17, 1998.
The American Society for Biochemistry and Molecular Biology, Inc.