Altered PYK2 phosphorylation by ANG II in hypertensive vascular smooth muscle.
Vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) exhibit increased cell growth compared with normotensive Wistar-Kyoto rats (WKY). ANG II stimulates growth via G(q)-protein-coupled signaling that involves changes in cytosolic intracellular Ca(2+) concentration ([Ca(2+)](i)) and activation of protein kinase C (PKC) and mitogen-activated protein kinases. This study examines the role of the proline-rich tyrosine kinase 2 (PYK2) in hypertensive VSMC. Basal PYK2 phosphorylation in SHR VSMC was increased compared with WKY (0.44 +/- 0.02 vs. 0.20 +/- 0.02-fold). ANG II-induced activation of PYK2 in SHR VSMC was of greater magnitude (2.2 +/- 0.2-fold in SHR; 1.4 +/- 0.1-fold in WKY) and occurred more rapidly (peak activation at 2 min in SHR vs. 5 min in WKY). This effect was blocked by pretreatment with the [Ca(2+)](i) chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid or the PKC inhibitor chelerythrine. Basal and ANG II-stimulated c-Fos expression was increased in SHR versus WKY VSMC. PYK2 downregulation with antisense oligonucleotides blocked ANG II-induced c-Fos expression. Increased PYK2 activation may be altered signaling cascades that regulate cell growth in hypertensive VSMC.
Rocic
Petra
P
Department of Physiology and Biophysics, University of Alabama at Birmingham, 35294, USA.
Griffin
Tina M
TM
McRae
Chastity N
CN
Lucchesi
Pamela A
PA
D000470:Alkaloids; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology; D053119:Benzophenanthridines; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051418:Focal Adhesion Kinase 2; D015870:Gene Expression / Q000502:physiology; D006973:Hypertension / Q000503:physiopathology*; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010617:Phenanthridines / Q000494:pharmacology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D051571:Protein Kinase C-alpha; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D000470:Alkaloids; D053119:Benzophenanthridines; D002614:Chelating Agents; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D016376:Oligonucleotides, Antisense; D010617:Phenanthridines; D016760:Proto-Oncogene Proteins c-fos; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D004533:Egtazic Acid; C016299:chelerythrine; D011505:Protein-Tyrosine Kinases; D051418:Focal Adhesion Kinase 2; C496054:Ptk2b protein, rat; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium