CYCLIC-AMP INHIBITION OF THROMBIN-INDUCED GROWTH IN VASCULAR SMOOTH-MUSCLE CELLS CORRELATES WITH DECREASED JNK1 ACTIVITY AND C-JUN EXPRESSION

Authors
Citation
Gn. Rao et Ms. Runge, CYCLIC-AMP INHIBITION OF THROMBIN-INDUCED GROWTH IN VASCULAR SMOOTH-MUSCLE CELLS CORRELATES WITH DECREASED JNK1 ACTIVITY AND C-JUN EXPRESSION, The Journal of biological chemistry, 271(34), 1996, pp. 20805-20810
Citations number
45
Categorie Soggetti
Biology
ISSN journal
00219258
Volume
271
Issue
34
Year of publication
1996
Pages
20805 - 20810
Database
ISI
SICI code
0021-9258(1996)271:34<20805:CIOTGI>2.0.ZU;2-U
Abstract
Thrombin is a potent modulator of vascular tone and vascular smooth mu scle cell (VSMC) mitogenesis. Early studies from other laboratories de monstrated that cyclic AMP (cAMP) antagonizes the mitogenic effects of platelet-derived growth factor and epidermal growth factor by inhibit ing the extracellular signal-regulated protein kinases (ERKs; p42, p44 ) group of mitogen-activated protein kinases (MAPKs) in several cell t ypes. This report examines the role of ERKs and Jun N-terminal kinase 1 (JNK1) groups of mitogen-activated protein kinases in thrombin-induc ed DNA synthesis in VSMCs using agents such as forskolin and dibutyryl cyclic AMP that increase intracellular cAMP levels, Both agents signif icantly inhibited thrombin-stimulated DNA synthesis in VSMCs, These ag ents, however, had no effect on thrombin induction of ERKs activation and c-Fos expression, suggesting divergence of the latter two events f rom the growth-signaling events of thrombin that are sensitive to inhi bition by cAMP. Thrombin activated JNK1 and induced c-Jun expression i n VSMCs in a time-dependent manner, In contrast to ERKs and c-Fos, thr ombin-induced JNK1 activation and c-Jun expression were sensitive to i nhibition by forskolin, suggesting an association of these events with thrombin-stimulated growth in these cells, Thrombin also increased AP -1 activity, and this response was significantly blunted by forskolin, Together, these results demonstrate a correlation between JNK1 activa tion and c-Jun expression by thrombin and their association with the m itogenic signaling events of thrombin in VSMCs.