ITAM-based interaction of ERM proteins with Syk mediates signaling by the leukocyte adhesion receptor PSGL-1.
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.
Urzainqui
Ana
A
Servicio de Inmunología, Hospital de la Princesa, Universidad Autónoma de Madrid, Madrid, Spain.
Serrador
Juan M
JM
Viedma
Fernando
F
Yáñez-Mó
María
M
Rodríguez
Antonio
A
Corbí
Angel L
AL
Alonso-Lebrero
Jose L
JL
Luque
Alfonso
A
Deckert
Marcel
M
Vázquez
Jesús
J
Sánchez-Madrid
Francisco
F
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
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