Exp Mol Med.  2006 Dec;38(6):703-717.

Tyrosine phosphatase and cytochrome P450 activity are critical in regulating store-operated calcium channels in human fibroblasts

• Lee KM

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.

Keyword

bradykinin; calcium channels; protein-tyrosine kinases; protein-tyrosine phosphatases

MeSH Terms

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