Abstract
We have studied modulation of "store-operated calcium influx" by tyrosine phosphatases in the pancreatic acinar cell line AR42J and in HEK 293 cells. We show that inhibition of tyrosine phosphatases by bis-(N,N-dimethyl-hydroxamido) hydrooxovanadate (DMHV) leads to an increase in Ca(2+) release-activated Ca(2+) (CRAC) entry. This effect can be blocked in the presence of 2-aminoethyldiphenyl borate (2-APB). Furthermore, transfection of HEK 293 cells with the human wild-type tyrosine phosphatase PTP1B leads to inhibition of CRAC influx, whereas transfection with the substrate-trapping mutant of PTP1B (D181A) slightly increases Ca(2+) influx. It also decreases enzymatic activity of PTP1B as compared to non-transfected cells. Our data suggest that CRAC influx is modulated by tyrosine phosphorylation and dephosphorylation which involves the tyrosine phosphatase PTP1B.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Bombesin / pharmacology
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Boron Compounds / pharmacology
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Calcium / metabolism*
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Calcium / pharmacology
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Calcium Channels / drug effects
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Calcium Channels / physiology*
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Cell Line
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Cell Line, Tumor
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Cytosol / chemistry
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Enzyme Inhibitors / pharmacology
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Humans
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Kinetics
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Microscopy, Confocal
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Microscopy, Fluorescence
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Muramidase / chemistry
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Muramidase / metabolism
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Mutagenesis, Site-Directed
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Mutation
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Phosphorylation
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Plasmids / genetics
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Protein Tyrosine Phosphatase, Non-Receptor Type 1
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Protein Tyrosine Phosphatases / drug effects
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Protein Tyrosine Phosphatases / genetics
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Protein Tyrosine Phosphatases / physiology*
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Rats
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Thapsigargin / pharmacology
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Transfection
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Vanadates / pharmacology
Substances
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Boron Compounds
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Calcium Channels
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Enzyme Inhibitors
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bis(N,N-dimethylhydroxamido)hydroxooxovanadate
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Vanadates
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Thapsigargin
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2-aminoethoxydiphenyl borate
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PTPN1 protein, human
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Protein Tyrosine Phosphatase, Non-Receptor Type 1
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Protein Tyrosine Phosphatases
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Ptpn1 protein, rat
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Muramidase
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Bombesin
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Calcium