Ca2+-sensitive tyrosine kinase Pyk2/CAK β-dependent signaling is essential for G-protein-coupled receptor agonist-induced hypertrophy
| Autor: | Kazuhiko Nishida, Hiroyuki Nakayama, Michio Asahi, Shungo Hikoso, Masatsugu Hori, Toshihiro Takeda, Tetsuya Watanabe, Yoshiharu Higuchi, Masayuki Taniike, Osamu Yamaguchi, Kazunori Kashiwase, Yasushi Matsumura, Ikuko Tsujimoto, Shinichi Hirotani, Kinya Otsu, Terukatsu Sasaki |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
rac1 GTP-Binding Protein
medicine.medical_specialty PTK2 Cardiomegaly Transfection Tropomyosin receptor kinase C Receptor tyrosine kinase Receptors G-Protein-Coupled Phenylephrine chemistry.chemical_compound Ca2+/calmodulin-dependent protein kinase Internal medicine medicine Animals Myocytes Cardiac Phosphorylation Phosphotyrosine Molecular Biology Cells Cultured Endothelin-1 biology Chemistry Tyrosine phosphorylation Protein-Tyrosine Kinases Rats Cell biology Enzyme Activation Focal Adhesion Kinase 2 Endocrinology Tyrosine kinase 2 Mutation biology.protein Calcium Reactive Oxygen Species Cardiology and Cardiovascular Medicine Tyrosine kinase Platelet-derived growth factor receptor Signal Transduction |
| Zdroj: | Journal of Molecular and Cellular Cardiology. 36:799-807 |
| ISSN: | 0022-2828 |
| DOI: | 10.1016/j.yjmcc.2004.03.002 |
| Popis: | G-protein-coupled receptor agonists including endothelin-1 (ET-1) and phenylephrine (PE) induce hypertrophy in neonatal ventricular cardiomyocytes. Others and we previously reported that Rac1 signaling pathway plays an important role in this agonist-induced cardiomyocyte hypertrophy. In this study reported here, we found that a Ca(2+)-sensitive non-receptor tyrosine kinase, proline-rich tyrosine kinase 2 (Pyk2)/cell adhesion kinase beta (CAKbeta), is involved in ET-1- and PE-induced cardiomyocyte hypertrophy medicated through Rac1 activation. ET-1, PE or the Ca(2+) inophore, ionomycin, stimulated a rapid increase in tyrosine phosphorylation of Pyk2. The tyrosine phosphorylation of Pyk2 was suppressed by the Ca(2+) chelator, BAPTA. ET-1- or PE-induced increases in [(3)H]-leucine incorporation and expression of atrial natriuretic factor and the enhancement of sarcomere organization. Infection of cardiomyocytes with an adenovirus expressing a mutant Pyk2 which lacked its kinase domain or its ability to bind to c-Src, eliminated ET-1- and PE-induced hypertrophic responses. Inhibition of Pyk2 activation also suppressed Rac1 activation and reactive oxygen species (ROS) production. These findings suggest that the signal transduction pathway leading to hypertrophy involves Ca(2+)-induced Pyk2 activation followed by Rac1-dependent ROS production. |
| Databáze: | OpenAIRE |
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