The PDZ-binding domain of syndecan-2 inhibits LFA-1 high-affinity conformation

Cell Signal. 2014 Jul;26(7):1489-99. doi: 10.1016/j.cellsig.2014.03.012. Epub 2014 Mar 21.

Abstract

Syndecans are cell membrane proteoglycans that can modulate the activity and dynamics of some growth factor receptors and integrins. Here, we show the down-regulation of integrin lymphocyte function-associated antigen-1 (LFA-1) and inhibition of adhesion of Jurkat T cells transfected with syndecan-2. The PDZ-binding domain in the cytoplasmic region of syndecan-2 was necessary to block the LFA-1 high-affinity conformation, and to reduce cellular adhesion. A second cytoplasmic motif comprising tyrosines 179 and 191, and serines 187 and 188 contributed also to reduce LFA-1 function and cellular adhesion. Inhibition of the LFA-1 high-affinity conformation by syndecan-2 was independent of the expression of the talin head domain and RhoA, Rac1 and Cdc42 GTPases. These results demonstrate the importance of PDZ-binding domain of syndecan-2 for controlling LFA-1 affinity and cell adhesion.

Keywords: Cell adhesion; Integrin; Proteoglycan; Talin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocytes / metabolism
  • Cell Adhesion / physiology*
  • Cell Line, Tumor
  • Cell Membrane / metabolism
  • Cell Movement
  • Down-Regulation
  • Endothelium / cytology
  • Endothelium / metabolism
  • GTPase-Activating Proteins / biosynthesis
  • Humans
  • Jurkat Cells
  • Lymphocyte Function-Associated Antigen-1 / biosynthesis*
  • Lymphocyte Function-Associated Antigen-1 / metabolism
  • PDZ Domains / genetics*
  • Phosphoproteins / biosynthesis
  • Protein Binding
  • Syndecan-2 / genetics
  • Syndecan-2 / metabolism*
  • T-Lymphocytes / metabolism
  • Talin / biosynthesis
  • Transfection
  • rac1 GTP-Binding Protein / biosynthesis
  • rhoA GTP-Binding Protein / biosynthesis

Substances

  • ARHGAP31 protein, human
  • GTPase-Activating Proteins
  • Lymphocyte Function-Associated Antigen-1
  • Phosphoproteins
  • RAC1 protein, human
  • SDC2 protein, human
  • Talin
  • Syndecan-2
  • rac1 GTP-Binding Protein
  • rhoA GTP-Binding Protein