ATP-induced focal adhesion kinase activity is negatively modulated by phospholipase D2 in PC12 cells.
- Author:
Yoe Sik BAE
1
;
Sung Ho RYU
Author Information
1. Division of Molecular and Life Sciences, Pohang University of Science and Technology, Korea.
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Focal adhesion kinase;
Phosphatidic acid;
Phospholipase D;
Paxillin;
Tyrosine phosphatase
- MeSH:
Adenosine Triphosphate/*metabolism;
Animal;
Culture Media, Serum-Free;
Cytoskeletal Proteins/metabolism;
Enzyme Activation/drug effects;
Enzyme Inhibitors/pharmacology;
Focal Adhesions/metabolism;
PC12 Cells;
Phospholipase D/*metabolism;
Phosphoproteins/metabolism;
Phosphorylation;
Propranolol/pharmacology;
Protein Kinase C/antagonists & inhibitors;
Protein-Tyrosine Kinase/*metabolism;
Rats;
Support, Non-U.S. Gov't;
Vasodilator Agents/pharmacology
- From:Experimental & Molecular Medicine
2001;33(3):150-155
- CountryRepublic of Korea
- Language:English
-
Abstract:
Extracellular ATP has been known to modulate various cellular responses including mitogenesis, secretion and morphogenic activity in neuronal cells. In the ATP-induced morphogenic activity, focal adhesion kinase(s) such as Fak have been suggested to play a critical role. Binding of ATP to its specific cell surface receptor in PC12 cells induces phospholipase D (PLD) activity. However, the role of PLD on ATP-induced Fak activation in PC12 cells remains unclear. In this study, we investigated the role of PLD on the ATP-induced Fak activation and paxillin phosphorylation using two established cell lines: wild type PLD2- and lipase-inactive mutant PLD2-inducible PC12 cells. Stimulation of cells with ATP caused PLD2 activation via classical protein kinase C activation. ATP also induced Fak activation, and paxillin phosphorylation, and were dramatically reduced by wild type PLD2 overexpression but not by lipase-inactive mutant PLD2 overexpression. When the PC12 cells were pretreated with propranolol, a specific inhibitor for phosphatidic acid phosphohydrolase resulting in the accumulation of PA, ATP-induced Fak activation and paxillin phosphorylation were also reduced. We found that inhibition of tyrosine phosphatases by pervanadate completely blocked PLD2-dependent Fak and paxillin dephosphorylation. Taken together, we suggest that PLD2 activity might play a negative role in ATP-induced Fak and paxillin phosphorylation possibly through tyrosine phosphatases.
