Tyrosine phosphatase PTP1B modulates store-operated calcium influx.
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.
Department of Physiology, University of the Saarland, Building 58, D-66421, Homburg/Saar, Germany.
Shyuefang
S
Hsu
Andreas
A
Schmid
Lutz
L
Sternfeld
Ines
I
Anderie
Gonzalo
G
Solis
Hans Werner
HW
Hofer
Irene
I
Schulz
D000818:Animals; D001839:Bombesin / Q000494:pharmacology; D001896:Boron Compounds / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D045744:Cell Line, Tumor; D003600:Cytosol / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009113:Muramidase / Q000737:chemistry / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D010766:Phosphorylation; D010957:Plasmids / Q000235:genetics; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D051381:Rats; D019284:Thapsigargin / Q000494:pharmacology; D014162:Transfection; D014638:Vanadates / Q000494:pharmacology
D001896:Boron Compounds; D015220:Calcium Channels; D004791:Enzyme Inhibitors; C402001:bis(N,N-dimethylhydroxamido)hydroxooxovanadate; D014638:Vanadates; D019284:Thapsigargin; C109986:2-aminoethoxydiphenyl borate; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; C516610:Ptpn1 protein, rat; D009113:Muramidase; D001839:Bombesin; D002118:Calcium