Lysophosphatidic Acid Stimulates p21-Activated Kinase in Vascular Smooth Muscle Cells

2002 ◽  
Vol 291 (3) ◽  
pp. 687-691 ◽  
Author(s):  
Udo Schmitz ◽  
Kerstin Thömmes ◽  
Imke Beier ◽  
Hans Vetter
2005 ◽  
Vol 289 (5) ◽  
pp. C1286-C1294 ◽  
Author(s):  
Elethia A. Woolfolk ◽  
Satoru Eguchi ◽  
Haruhiko Ohtsu ◽  
Hidekatsu Nakashima ◽  
Hikaru Ueno ◽  
...  

ANG II promotes remodeling of vascular smooth muscle cells (VSMCs) in cardiovascular diseases. It has been shown to activate p21-activated kinase (PAK)1, a critical component of signaling pathways implicated in growth and migration. However, the detailed signaling mechanism by which ANG II induces PAK1 activation in VSMCs remains unclear. Therefore, we have examined the mechanism required for activation of PAK1 by ANG II in VSMCs. ANG II, through activation of the ANG II type 1 receptor, rapidly promotes phosphorylation of PAK1 in VSMCs via a pathway independent of transactivation of the epidermal growth factor receptor. Using selective agonists and inhibitors, we demonstrated that mobilization of intracellular Ca2+ and PKCδ activation are required for ANG II-induced PAK1 phosphorylation. Rottlerin, a PKCδ inhibitor, significantly blocked ANG II-induced PAK1 phosphorylation. Further support for this notion was provided through infection of VSMCs with adenovirus encoding a dominant-negative (dn)PKCδ, which also markedly reduced phosphorylation of PAK1 by ANG II. In this pathway, Ca2+ acts upstream of PKCδ because a Ca2+ ionophore rapidly induced PKCδ phosphorylation at Tyr311 and Ca2+-dependent PAK1 phosphorylation was blocked by rottlerin. In addition, dnPYK-2, dnRac, and antioxidants inhibited ANG II-induced PAK1 phosphorylation, suggesting that PYK-2, Rac, and reactive oxygen species are involved in the upstream signaling. Finally, dnPAK1 markedly inhibited ANG II-induced protein synthesis in VSMCs. These data provide a novel signaling pathway by which ANG II may contribute to vascular remodeling.


2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Marius Catalin Staiculescu ◽  
Zhongkui Hong ◽  
Zhe Sun ◽  
Francisco Ramirez‐Perez ◽  
Gerald A. Meininger ◽  
...  

1999 ◽  
Vol 94 (5) ◽  
pp. 317-326 ◽  
Author(s):  
Isabelle Gennero ◽  
Jean-Marie Xuereb ◽  
Marie-Françoise Simon ◽  
Jean-Pierre Girolami ◽  
Jean-Louis Bascands ◽  
...  

1998 ◽  
Vol 82 (12) ◽  
pp. 1272-1278 ◽  
Author(s):  
Udo Schmitz ◽  
Takafumi Ishida ◽  
Mari Ishida ◽  
James Surapisitchat ◽  
Mohammed I. Hasham ◽  
...  

2003 ◽  
Vol 41 (3) ◽  
pp. 381-387 ◽  
Author(s):  
Yan-Jun Xu ◽  
Satyajeet S. Rathi ◽  
Donald C. Chapman ◽  
Amarjit S. Arneja ◽  
Naranjan S. Dhalla

Cell Calcium ◽  
2005 ◽  
Vol 38 (6) ◽  
pp. 569-579 ◽  
Author(s):  
Yan-Jun Xu ◽  
Harjot K. Saini ◽  
Sukhinder K. Cheema ◽  
Naranjan S. Dhalla

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