Tyrosine phosphatase and cytochrome P450 activity are critical in regulating store-operated calcium channels in human fibroblasts.
- Author:
Kyung Mi LEE
1
,
2
Author Information
1. Department of Biochemistry and Division of Brain Korea 21 Program for Biomedical Science, Korea University College of Medicine, Seoul 136-705, Korea. kyunglee@korea.ac.kr (KML)
2. mitch@drugs.bsd.uchicago.edu (MLV)
- Publication Type:Original Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
- Keywords:
bradykinin;
calcium channels;
protein-tyrosine kinases;
protein-tyrosine phosphatases
- MeSH:
Vanadates/pharmacology;
Tetradecanoylphorbol Acetate/pharmacology;
Protein-Tyrosine-Phosphatase/*metabolism;
Phosphotyrosine/metabolism;
Phosphorylation/drug effects;
Nitric Oxide/metabolism;
Humans;
Fibroblasts;
Epidermal Growth Factor/pharmacology;
Enzyme Inhibitors/pharmacology;
Econazole/pharmacology;
Cytochrome P-450 Enzyme System/antagonists & inhibitors/*metabolism;
Cyclic GMP/analogs & derivatives/metabolism;
Cells, Cultured;
Calcium Channels/*metabolism;
Calcium/metabolism;
Bradykinin/pharmacology
- From:Experimental & Molecular Medicine
2006;38(6):703-717
- CountryRepublic of Korea
- Language:English
-
Abstract:
Diverse signaling pathways have been proposed to regulate store-operated calcium entry (SOCE) in a wide variety of cell types. However, it still needs to be determined if all of these known pathways operate in a single cell type. In this study, we examined involvement of various signaling molecules in SOCE using human fibroblast cells (HSWP). Bradykinin (BK)-stimulated Ca2+ entry, previously shown to be via SOCE, is enhanced by the addition of vanadate, an inhibitor of tyrosine phosphatases. Furthermore, SOCE is regulated by cytochrome P-450, as demonstrated by the fact that the products of cytochrome P-450 activity (14,15 EET) stimulated SOCE while econazole, an inhibitor of cytochrome P450, suppressed BK-stimulated Ca2+ entry. In contrast, Ca2+ entry was unaffected by the guanylate cyclase inhibitor LY83583, or the membrane permeant cyclic GMP analog 8-bromo-cyclic GMP (8-Br-cGMP). Neither nitric oxide donors nor phorbol esters affected BK-stimulated Ca2+ entry. SOCE in HSWP cells is primarily regulated by tyrosine phosphorylation and the cytochrome P-450 pathway, but not by cyclic GMP, nitric oxide, or protein kinase C. Thus, multiple pathways do operate in a single cell type leading to the activation of Ca2+ entry and some of these signaling pathways are more prominently involved in regulating calcium entry in different cell types.
