Expression of Protein Tyrosine Phosphatase-Like Molecule ICA512/IA-2 Induces Growth Arrest in Yeast Cells and Transfected Mammalian Cell Lines

J Autoimmun. 2001 Aug;17(1):51-61. doi: 10.1006/jaut.2001.0516.

Abstract

The ICA512/IA-2 molecule, a protein with similarity to receptor-type protein tyrosine phosphatases, was discovered during studies to identify autoantigens in Type 1 diabetes. The biological function of ICA512/IA-2 is unknown. We describe striking effects of ICA512/IA-2 on viability and growth of both yeast cells and cultured mammalian cells. In transformed yeast Saccharomyces cerevisiae cells, expression of ICA512/IA-2 induced growth retardation as judged by measurements of optical density and counts of colony-forming units. In contrast, expression of the intracellular domain (amino acids 600-979) of ICA512/IA-2 in yeast or mammalian cells had no such effects. In investigations on apoptosis, expression of ICA512/IA-2 in yeast cells caused loss of plasma membrane asymmetry, but not release of cytochrome c from mitochondria which did occur in a control system after expression of the pro-apoptotic molecule Bax. Possible interactions between ICA512/IA-2 and components of the cytoskeleton were not supported by studies on staining of fixed yeast cells with phalloidin-Texas Red. With transfected mammalian cell lines COS-7 and NIH3T3, expression of ICA512/IA-2 likewise induced growth arrest, with some of the morphological features of apoptosis. Thus obligatory expression of ICA512/IA-2 in eukaryotic cells causes disruption of cellular activities, with growth arrest in yeast and nuclear pycnosis/fragmentation in mammalian cells. A possible explanation is that growth inhibition reflects a part of the presently unknown function of ICA512/IA-2.

MeSH terms

  • 3T3 Cells / cytology
  • 3T3 Cells / enzymology
  • 3T3 Cells / immunology
  • Animals
  • Autoantigens / biosynthesis*
  • Autoantigens / genetics
  • Autoantigens / physiology
  • COS Cells / cytology
  • COS Cells / enzymology
  • Cell Line
  • Cell Size
  • Cell Survival
  • Colony Count, Microbial
  • Cytochrome c Group / metabolism
  • Growth Inhibitors / biosynthesis*
  • Growth Inhibitors / genetics
  • Growth Inhibitors / physiology
  • Membrane Proteins / biosynthesis*
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology
  • Mice
  • Phalloidine / analysis
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Protein Tyrosine Phosphatases / biosynthesis*
  • Protein Tyrosine Phosphatases / genetics
  • Protein Tyrosine Phosphatases / physiology
  • Receptor-Like Protein Tyrosine Phosphatases, Class 8
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae / genetics*
  • Staining and Labeling
  • Transfection* / methods

Substances

  • Autoantigens
  • Cytochrome c Group
  • Growth Inhibitors
  • Membrane Proteins
  • Phalloidine
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Protein Tyrosine Phosphatases
  • Ptprn protein, mouse
  • Receptor-Like Protein Tyrosine Phosphatases, Class 8