title: ITAM-based interaction of ERM proteins with Syk mediates signaling by the leukocyte adhesion receptor PSGL-1.
abstract: P-selectin glycoprotein ligand 1 (PSGL-1) is a leukocyte adhesion molecule involved in cell tether and rolling on activated endothelium. Our work shows that PSGL-1 associates with Syk. This association is mediated by the actin-linking proteins moesin and ezrin, which directly interact with Syk in an ITAM-dependent manner. PSGL-1 engagement induces tyrosine phosphorylation of Syk and SRE-dependent transcriptional activity. Treatment of cells with the Syk inhibitor piceatannol and overexpression of either a Syk dead kinase mutant or an ITAM-mutated moesin abrogated PSGL-1-induced transcriptional activation. These data unveil a new functional role for the ERMs (ezrin/radixin/moesin) as adaptor molecules in the interactions of adhesion receptors and intracellular tyrosine kinases and show that PSGL-1 is a signaling molecule in leukocytes.
authors.affiliation: Servicio de Inmunología, Hospital de la Princesa, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Urzainqui
authors.forename: Juan M
authors.initials: JM
authors.lastname: Serrador
authors.forename: Fernando
authors.initials: F
authors.lastname: Viedma
authors.forename: María
authors.initials: M
authors.lastname: Yáñez-Mó
authors.forename: Antonio
authors.initials: A
authors.lastname: Rodríguez
authors.forename: Angel L
authors.initials: AL
authors.lastname: Corbí
authors.forename: Jose L
authors.initials: JL
authors.lastname: Alonso-Lebrero
authors.forename: Alfonso
authors.initials: A
authors.lastname: Luque
authors.forename: Marcel
authors.initials: M
authors.lastname: Deckert
authors.forename: Jesús
authors.initials: J
authors.lastname: Vázquez
authors.forename: Francisco
authors.initials: F
authors.lastname: Sánchez-Madrid
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D004792:Enzyme Precursors / Q000737:chemistry / Q000502:physiology*; D018922:HL-60 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D036904:Leukocyte Rolling; D007962:Leukocytes / Q000502:physiology*; D008024:Ligands; D008562:Membrane Glycoproteins / Q000502:physiology*; D008840:Microfilament Proteins / Q000235:genetics / Q000502:physiology; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000502:physiology*; D015398:Signal Transduction; D000072377:Syk Kinase; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D015533:Transcriptional Activation; D014443:Tyrosine / Q000737:chemistry; D020298:U937 Cells
chemical_list: D004268:DNA-Binding Proteins; C086680:ETV5 protein, human; D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; C084882:P-selectin ligand protein; D014157:Transcription Factors; C071058:moesin; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase