RIFLE: a novel ring zinc finger-leucine-rich repeat containing protein, regulates select cell adhesion molecules in PC12 cells

J Cell Biochem. 2003 Dec 15;90(6):1224-41. doi: 10.1002/jcb.10674.

Abstract

Cell adhesion molecules play a critical role in cell contacts, whether cell-cell or cell-matrix, and are regulated by multiple signaling pathways. In this report, we identify a novel ring zinc finger-leucine-rich repeat containing protein (RIFLE) and show that RIFLE, expressed in PC12 cells, enhances the Serine (Ser)21/9 phosphorylation of glycogen synthase kinase-3alpha/beta (GSK-3alpha/beta) resulting in the inhibition of GSK-3 kinase activity and increase of beta-catenin levels. RIFLE expression also is associated with elevated E-cadherin protein levels but not N-cadherin. The regulation of these cell adhesion-associated molecules by RIFLE is accompanied by a significant increase in cell-cell and cell-matrix adhesion. Moreover, increase in cell-cell adhesion but not cell-matrix adhesion by RIFLE can be mimicked by selective inhibition of GSK-3. Our results suggest that RIFLE represents a novel signaling protein that mediates components of the Wnt/wingless signaling pathway and cell adhesion in PC12 cells.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cadherins / metabolism*
  • Calcium / metabolism
  • Cell Adhesion Molecules / chemistry
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Collagen Type IV / metabolism
  • Cytoskeletal Proteins / metabolism*
  • Fibronectins / metabolism
  • Glycogen Synthase Kinase 3 / genetics
  • Glycogen Synthase Kinase 3 / metabolism*
  • Glycogen Synthase Kinase 3 beta
  • Humans
  • Leucine-Rich Repeat Proteins
  • Molecular Sequence Data
  • PC12 Cells*
  • Phosphorylation
  • Proteins / genetics
  • Proteins / metabolism*
  • Proto-Oncogene Proteins / metabolism
  • Rats
  • Sequence Alignment
  • Signal Transduction / physiology
  • Tissue Distribution
  • Trans-Activators / metabolism*
  • Wnt Proteins
  • Zinc Fingers
  • beta Catenin

Substances

  • CTNNB1 protein, human
  • Cadherins
  • Cell Adhesion Molecules
  • Collagen Type IV
  • Ctnnb1 protein, rat
  • Cytoskeletal Proteins
  • Fibronectins
  • Leucine-Rich Repeat Proteins
  • Proteins
  • Proto-Oncogene Proteins
  • RIFLE protein, rat
  • Trans-Activators
  • Wnt Proteins
  • beta Catenin
  • Glycogen Synthase Kinase 3 beta
  • Glycogen Synthase Kinase 3
  • glycogen synthase kinase 3 alpha
  • Calcium