RGD Reference Report - Ca(2+)-sensitive tyrosine kinase Pyk2/CAK beta-dependent signaling is essential for G-protein-coupled receptor agonist-induced hypertrophy. - Rat Genome Database

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Ca(2+)-sensitive tyrosine kinase Pyk2/CAK beta-dependent signaling is essential for G-protein-coupled receptor agonist-induced hypertrophy.

Authors: Hirotani, S  Higuchi, Y  Nishida, K  Nakayama, H  Yamaguchi, O  Hikoso, S  Takeda, T  Kashiwase, K  Watanabe, T  Asahi, M  Taniike, M  Tsujimoto, I  Matsumura, Y  Sasaki, T  Hori, M  Otsu, K 
Citation: Hirotani S, etal., J Mol Cell Cardiol. 2004 Jun;36(6):799-807.
RGD ID: 1642626
Pubmed: PMID:15158121   (View Abstract at PubMed)
DOI: DOI:10.1016/j.yjmcc.2004.03.002   (Journal Full-text)

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.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Ptk2bRatactivation of GTPase activity  IMP  RGD 
Ptk2bRatpositive regulation of cell growth  IMP  RGD 
Ptk2bRatpositive regulation of reactive oxygen species metabolic process  IMP  RGD 

Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations


  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Ptk2bRatRho/Rac/Cdc42 mediated signaling pathway  IMP  RGD 
Objects Annotated

Genes (Rattus norvegicus)
Ptk2b  (protein tyrosine kinase 2 beta)


Additional Information