ITAM-based interaction of ERM proteins with Syk mediates signaling by the leukocyte adhesion receptor PSGL-1

Immunity. 2002 Oct;17(4):401-12. doi: 10.1016/s1074-7613(02)00420-x.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Base Sequence
  • Binding Sites
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Enzyme Precursors / chemistry
  • Enzyme Precursors / physiology*
  • HL-60 Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Leukocyte Rolling
  • Leukocytes / physiology*
  • Ligands
  • Membrane Glycoproteins / physiology*
  • Microfilament Proteins / genetics
  • Microfilament Proteins / physiology
  • Molecular Sequence Data
  • Phosphorylation
  • Protein-Tyrosine Kinases / chemistry
  • Protein-Tyrosine Kinases / physiology*
  • Signal Transduction
  • Syk Kinase
  • Transcription Factors / chemistry
  • Transcription Factors / genetics
  • Transcription Factors / physiology*
  • Transcriptional Activation
  • Tyrosine / chemistry
  • U937 Cells

Substances

  • DNA-Binding Proteins
  • ETV5 protein, human
  • Enzyme Precursors
  • Intracellular Signaling Peptides and Proteins
  • Ligands
  • Membrane Glycoproteins
  • Microfilament Proteins
  • P-selectin ligand protein
  • Transcription Factors
  • moesin
  • Tyrosine
  • Protein-Tyrosine Kinases
  • SYK protein, human
  • Syk Kinase