title: The adaptor protein SAP directly associates with PECAM-1 and regulates PECAM-1-mediated-cell adhesion in T-like cell lines.
abstract: SAP is a small cytosolic adaptor protein expressed in hematopoietic lineages whose main function is to regulate intracellular signaling pathways induced by the triggering of members of the SLAM receptor family. In this paper, we have identified the adhesion molecule PECAM-1 as a new partner for SAP in a conditional yeast two-hybrid screen. PECAM-1 is an immunoglobulin-like molecule expressed by endothelial cells and leukocytes, which possesses both pro- and anti-inflammatory properties. However, little is known about PECAM-1 functions in T cells. We show that SAP directly and specifically interacts with the cytosolic tyrosine 686 of PECAM-1. We generated different T-like cell lines in which SAP or PECAM-1 are expressed or down modulated and we demonstrate that a diminished SAP expression correlates with a diminished PECAM-1-mediated adhesion. Although SAP has mainly been shown to associate with SLAM receptors, we evidence here that SAP is a new actor downstream of PECAM-1.
authors.affiliation: Université Paris-Sud, Orsay F-91405, France; INSERM UMR-S 1004, Hôpital Paul Brousse, 14-16 Av Paul Vaillant Couturier, Villejuif F-94807, France; INSERM UMR-S U972, Hôpital Paul Brousse, 14-16 Av Paul Vaillant Couturier, Villejuif F-94807, France. Electronic address: richard.proust@inserm.fr.
authors.forename: Richard
authors.initials: R
authors.lastname: Proust
authors.affiliation: INSERM UMR-S 749, Institut Gustave Roussy, Pavillon de Recherche II, 114 rue Edouard Vaillant, Villejuif F-94805, France. Electronic address: catherine.crouin@inserm.fr.
authors.forename: Catherine
authors.initials: C
authors.lastname: Crouin
authors.affiliation: Université Paris-Sud, Orsay F-91405, France; Institut Curie, Normal and Pathological Development of Melanocytes, 91405 Orsay, France; CNRS, UMR3347, Bat 110, 91405 Orsay, France; INSERM UMR-S1021, Bat 110, 91405 Orsay, France; INSERM UMR-S 1004, Hôpital Paul Brousse, 14-16 Av Paul Vaillant Couturier, Villejuif F-94807, France. Electronic address: yewakon.gandji@u-psud.fr.
authors.forename: Leslie Yewakon
authors.initials: LY
authors.lastname: Gandji
authors.affiliation: INSERM UMR-S 749, Institut Gustave Roussy, Pavillon de Recherche II, 114 rue Edouard Vaillant, Villejuif F-94805, France. Electronic address: jacques.bertoglio@igr.fr.
authors.forename: Jacques
authors.initials: J
authors.lastname: Bertoglio
authors.affiliation: Université Paris-Sud, Orsay F-91405, France; Institut Curie, Normal and Pathological Development of Melanocytes, 91405 Orsay, France; CNRS, UMR3347, Bat 110, 91405 Orsay, France; INSERM UMR-S1021, Bat 110, 91405 Orsay, France; INSERM UMR-S 1004, Hôpital Paul Brousse, 14-16 Av Paul Vaillant Couturier, Villejuif F-94807, France. Electronic address: franck.gesbert@curie.fr.
authors.forename: Franck
authors.initials: F
authors.lastname: Gesbert
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002448:Cell Adhesion; D002460:Cell Line; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism*; D019169:Jurkat Cells; D008969:Molecular Sequence Data; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D013601:T-Lymphocytes / Q000502:physiology*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; C114953:SH2D1A protein, human; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein
keywords: CAM; FCS; ITIM; ITSM; PECAM-1; SAP; SH2; SH2-containing tyrosine phosphatase-2; SH2-domain; SHP-2; SLAM; SLAM-associated protein; Src homology 2; T cell adhesion; TEM; X-linked lymphoproliferative syndrome-1; XLP-1; cell-adhesion-molecule; fetal calf serum; immunoreceptor tyrosine-based inhibition motif; immunoreceptor tyrosine-based switch motif; platelet–endothelial cell adhesion molecule-1; signaling lymphocyte activation molecule; transendothelial migration