Unique regulation of c-Jun N-terminal kinase by PYK2/CAK-beta in angiotensin II-stimulated vascular smooth muscle cells.

Frank GD, Eguchi S, Motley ED, Sasaki T, Inagami T
Biochem Biophys Res Commun. 2001 286 (4): 692-6

PMID: 11520052 · DOI:10.1006/bbrc.2001.5463

Activation of tyrosine kinases is believed to play a central role in angiotensin II (AngII) signaling. Here, we have investigated whether a tyrosine kinase, PYK2, is functionally involved in AngII-induced c-Jun N-terminal kinase (JNK) activation in vascular smooth muscle cells (VSMCs). Adenovirus expressing PYK2 kinase-inactive mutant K457A or a tyrosine phosphorylation site mutant Y402F was transfected in VSMCs. AngII-induced JNK phosphorylation was markedly enhanced by K457A, whereas it was suppressed by Y402F. Protein synthesis induced by AngII was also enhanced by K457A and inhibited by Y402F. In this regard, K457A suppressed PYK2 kinase activation by AngII, whereas it enhanced AngII-induced PYK2 Tyr(402) phosphorylation. By contrast, Y402F inhibited PYK2 Tyr(402) phosphorylation, whereas it markedly enhanced AngII-induced PYK2 kinase activation. Thus, we conclude that PYK2 kinase activity negatively regulates JNK activation and protein synthesis, whereas Tyr(402) phosphorylation positively regulates these events in AngII-stimulated VSMCs, suggesting a unique role of PYK2 in mediating vascular remodeling.

Copyright 2001 Academic Press.

MeSH Terms (18)

Adenoviridae Angiotensin II Animals Cells, Cultured Focal Adhesion Kinase 2 Genetic Vectors JNK Mitogen-Activated Protein Kinases Leucine Mitogen-Activated Protein Kinases Models, Biological Muscle, Smooth, Vascular Mutation Phosphorylation Phosphotyrosine Protein-Tyrosine Kinases Rats Rats, Sprague-Dawley Transfection

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