Inhibition of protein tyrosine phosphatase 1B by reactive oxygen species leads to maintenance of Ca2+ influx following store depletion in HEK 293 cells

Bogeski, Ivan and Bozem, Monika and Sternfeld, Lutz and Hofer, Hans Werner and Schulz, Irene (2006) Inhibition of protein tyrosine phosphatase 1B by reactive oxygen species leads to maintenance of Ca2+ influx following store depletion in HEK 293 cells. Cell Calcium, 40 (1). pp. 1-10. ISSN 01434160

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Abstract

Depletion of inositol 1,4,5 trisphosphate-sensitive Ca2+ stores generates a yet unknown signal, which leads to increase in Ca2+ influx
in different cell types [J.W. Putney Jr., A model for receptor-regulated calcium entry, Cell Calcium 7 (1986) 1–12]. Here, we describe a
mechanism that modulates this store-operated Ca2+ entry (SOC). Ca2+ influx leads to inhibition of protein tyrosine phosphatase 1B (PTP1B)
activity in HEK 293 cells [L. Sternfeld, et al., Tyrosine phosphatase PTP1B interacts with TRPV6 in vivo and plays a role in TRPV6-mediated
calcium influx in HEK293 cells, Cell Signal 17 (2005) 951–960]. Since Ca2+ does not directly inhibit PTP1B, we assumed an intermediate
signal, which links the rise in cytosolic Ca2+ concentration and PTP1B inhibition.We now show that Ca2+ influx is followed by generation of
reactive oxygen species (ROS) and that it is reduced in cells preincubated with catalase. Furthermore, Ca2+-dependent inhibition of PTP1B
can be abolished in the presence of catalase. H2O2 (100�M) directly added to cells inhibits PTP1B and leads to increase in Ca2+ influx after
store depletion. PP1, an inhibitor of the Src family tyrosine kinases, prevents H2O2-induced Ca2+ influx.
Our results show that ROS act as fine tuning modulators of Ca2+ entry. We assume that the Ca2+ influx channel or a protein involved in
its regulation remains tyrosine phosphorylated as a consequence of PTP1B inhibition by ROS. This leads to maintained Ca2+ influx in the
manner of a positive feedback loop.

Item Type:	Article
Subjects:	Medical and Health Sciences > Basic medicine Medical and Health Sciences > Health sciences
Divisions:	Faculty of Medical Science
Depositing User:	Ivan Bogeski
Date Deposited:	27 Nov 2012 10:44
Last Modified:	27 Nov 2012 10:44
URI:	https://eprints.ugd.edu.mk/id/eprint/2200

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