Expression of protein tyrosine phosphatase-like molecule ICA512/IA-2 induces growth arrest in yeast cells and transfected mammalian cell lines.
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.
Papakonstantinou
T
T
Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3168, Australia.
Myers
M A
MA
Jois
J
J
Roucou
X
X
Prescott
M
M
Rowley
M J
MJ
Mackay
I R
IR
D016475:3T3 Cells / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D000818:Animals; D001324:Autoantigens / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D019556:COS Cells / Q000166:cytology / Q000201:enzymology; D002460:Cell Line; D048429:Cell Size; D002470:Cell Survival; D015169:Colony Count, Microbial; D003574:Cytochrome c Group / Q000378:metabolism; D006131:Growth Inhibitors / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D051379:Mice; D010590:Phalloidine / Q000032:analysis; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000201:enzymology* / Q000235:genetics*; D013194:Staining and Labeling; D014162:Transfection / Q000379:methods
D001324:Autoantigens; D003574:Cytochrome c Group; D006131:Growth Inhibitors; D008565:Membrane Proteins; D010590:Phalloidine; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; C516863:Ptprn protein, mouse; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8