ITAM-Based Interaction of ERM Proteins with Syk Mediates Signaling by the Leukocyte Adhesion Receptor PSGL-1

• Published in: Immunity (Cambridge, Mass.) Vol. 17; no. 4; pp. 401 - 412
• Main Authors: Urzainqui, Ana, Serrador, Juan M, Viedma, Fernando, Yáñez-Mó, Marı́a, Rodrı́guez, Antonio, Corbı́, Angel L, Alonso-Lebrero, Jose L, Luque, Alfonso, Deckert, Marcel, Vázquez, Jesús, Sánchez-Madrid, Francisco
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-10-2002; Elsevier Limited
• Subjects: Amino Acid Motifs; Amino Acid Sequence; Base Sequence; Binding Sites; DNA-Binding Proteins - chemistry; DNA-Binding Proteins - genetics; DNA-Binding Proteins - physiology; Endothelium; Enzyme Precursors - chemistry; Enzyme Precursors - physiology; Experiments; Gene expression; Grants; HL-60 Cells; Humans; Intracellular Signaling Peptides and Proteins; Kinases; Leukocyte Rolling; Leukocytes; Leukocytes - physiology; Ligands; Membrane Glycoproteins - physiology; Microfilament Proteins - genetics; Microfilament Proteins - physiology; Molecular Sequence Data; Phosphorylation; Polymerase chain reaction; Protein-Tyrosine Kinases - chemistry; Protein-Tyrosine Kinases - physiology; Proteins; Recruitment; Rodents; Signal Transduction; Syk Kinase; Transcription Factors - chemistry; Transcription Factors - genetics; Transcription Factors - physiology; Transcriptional Activation; Tyrosine - chemistry; U937 Cells
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/S1074-7613(02)00420-X

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.