Effects of nonselective cation channels and PI3K on endothelin-1-induced PYK2 tyrosine phosphorylation in C6 glioma cells.

Abstract

We recently demonstrated that endothelin-1 (ET-1) activates two types of Ca2+-permeable nonselective cation channels (designated NSCC-1 and NSCC-2) in C6 glioma cells. In the present study, we investigated the effects of NSCCs on the ET-1-induced proline-rich tyrosine kinase 2 (PYK2) phosphorylation in C6 glioma cells. In addition, we examined the effects of phosphoinositide 3-kinase (PI3K) on the ET-1-induced NSCCs activation and PYK2 phosphorylation. The PI3K inhibitors wortmannin and LY-294002 inhibited ET-1-induced Ca2+ influx through NSCC-2 but not NSCC-1. On the other hand, addition of these inhibitors after stimulation with ET-1 failed to suppress Ca2+ influx through NSCC-2. PYK2 phosphorylation was abolished by blocking Ca2+ influx through NSCCs. The PI3K inhibitors blocked the NSCC-2-dependent part of ET-1-induced PYK2 phosphorylation. These results indicate that 1) NSCC-2 is stimulated by ET-1 via a PI3K-dependent cascade, whereas NSCC-1 is stimulated via a PI3K-independent cascade; 2) PI3K seems to be required for the activation of the Ca2+ entry, but not for its maintenance; 3) Ca2+ influx through NSCC-1 and NSCC-2 plays an essential role in ET-1-induced PYK2 phosphorylation; and 4) PI3K is involved in the ET-1-induced PYK2 phosphorylation that depends on the Ca2+ influx through NSCC-2.

• Authors: Yoshifumi Kawanabe, Nobuo Hashimoto, Tomoh Masaki
• Journal: American journal of physiology. Cell physiology (Am J Physiol Cell Physiol) Vol. 285 Issue 3 Pg. C539-45 (Sep 2003) ISSN: 0363-6143 [Print] United States
• PMID: 12900387 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Androstadienes
• Calcium Channel Blockers
• Calcium Channels
• Cations
• Chromones
• Endothelin-1
• Enzyme Inhibitors
• Imidazoles
• Inositol 1,4,5-Trisphosphate Receptors
• Ion Channels
• Morpholines
• Phosphoinositide-3 Kinase Inhibitors
• Receptors, Cytoplasmic and Nuclear
• 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
• Protein-Tyrosine Kinases
• Focal Adhesion Kinase 2
• Ptk2b protein, rat
• 1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole
• Calcium
• Wortmannin

Topics

• Androstadienes (pharmacology)
• Animals
• Calcium (metabolism)
• Calcium Channel Blockers (pharmacology)
• Calcium Channels (metabolism)
• Cations (metabolism)
• Cell Division (physiology)
• Chromones (pharmacology)
• Endothelin-1 (pharmacology)
• Enzyme Inhibitors (pharmacology)
• Focal Adhesion Kinase 2
• Glioma
• Imidazoles (pharmacology)
• Inositol 1,4,5-Trisphosphate Receptors
• Ion Channels (antagonists & inhibitors, metabolism)
• Morpholines (pharmacology)
• Phosphatidylinositol 3-Kinases (metabolism)
• Phosphoinositide-3 Kinase Inhibitors
• Phosphorylation (drug effects)
• Protein-Tyrosine Kinases (metabolism)
• Rats
• Receptors, Cytoplasmic and Nuclear (antagonists & inhibitors, metabolism)
• Tumor Cells, Cultured
• Wortmannin