Cyclic AMP inhibition of thrombin-induced growth in vascular smooth muscle cells correlates with decreased JNK1 activity and c-Jun expression

被引:60
作者
Rao, GN
Runge, MS
机构
[1] Division of Cardiology, University of Texas, Medical Branch, Galveston
[2] Division of Cardiology, University of Texas, Medical Branch, Galveston, TX 77555-1064
关键词
D O I
10.1074/jbc.271.34.20805
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Thrombin is a potent modulator of vascular tone and vascular smooth muscle cell (VSMC) mitogenesis. Early studies from other laboratories demonstrated that cyclic AMP (cAMP) antagonizes the mitogenic effects of platelet-derived growth factor and epidermal growth factor by inhibiting the extracellular signal-regulated protein kinases (ERKs; p42, p44) group of mitogen-activated protein kinases (MAPKs) in several cell types. This report examines the role of ERKs and Jun N-terminal kinase 1 (JNK1) groups of mitogen-activated protein kinases in thrombin-induced DNA synthesis in VSMCs using agents such as forskolin and dibutyrylcyclic AMP that increase intracellular cAMP levels, Both agents significantly inhibited thrombin-stimulated DNA synthesis in VSMCs, These agents, however, had no effect on thrombin induction of ERKs activation and c-Fos expression, suggesting divergence of the latter two events from the growth-signaling events of thrombin that are sensitive to inhibition by cAMP. Thrombin activated JNK1 and induced c-Jun expression in VSMCs in a time-dependent manner, In contrast to ERKs and c-Fos, thrombin-induced JNK1 activation and c-Jun expression were sensitive to inhibition 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 activation and c-Jun expression by thrombin and their association with the mitogenic signaling events of thrombin in VSMCs.
引用
收藏
页码:20805 / 20810
页数:6
相关论文
共 45 条
[1]   THE ROLE OF JUN, FOS AND THE AP-1 COMPLEX IN CELL-PROLIFERATION AND TRANSFORMATION [J].
ANGEL, P ;
KARIN, M .
BIOCHIMICA ET BIOPHYSICA ACTA, 1991, 1072 (2-3) :129-157
[2]  
BEEBE SJ, 1994, SEMIN CANCER BIOL, V5, P285
[3]   GROWTH-RELATED RESPONSES IN ARTERIAL SMOOTH-MUSCLE CELLS ARE ARRESTED BY THROMBIN RECEPTOR ANTISENSE SEQUENCES [J].
CHAIKOF, EL ;
CABAN, R ;
YAN, CN ;
RAO, GN ;
RUNGE, MS .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (13) :7431-7436
[4]   INHIBITION BY CAMP OF RAS-DEPENDENT ACTIVATION OF RAF [J].
COOK, SJ ;
MCCORMICK, F .
SCIENCE, 1993, 262 (5136) :1069-1072
[5]   TRANSFORMING G-PROTEIN-COUPLED RECEPTORS POTENTLY ACTIVATE JNK (SAPK) - EVIDENCE FOR A DIVERGENCE FROM THE TYROSINE KINASE SIGNALING PATHWAY [J].
COSO, OA ;
CHIARIELLO, R ;
KALINEC, G ;
KYRIAKIS, JM ;
WOODGETT, J ;
GUTKIND, JS .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (10) :5620-5624
[6]   FOS AND JUN - THE AP-1 CONNECTION [J].
CURRAN, T ;
FRANZA, BR .
CELL, 1988, 55 (03) :395-397
[7]  
DAVIS RJ, 1993, J BIOL CHEM, V268, P14553
[8]   MAPKS - NEW JNK EXPANDS THE GROUP [J].
DAVIS, RJ .
TRENDS IN BIOCHEMICAL SCIENCES, 1994, 19 (11) :470-473
[9]   JNK1 - A PROTEIN-KINASE STIMULATED BY UV-LIGHT AND HA-RAS THAT BINDS AND PHOSPHORYLATES THE C-JUN ACTIVATION DOMAIN [J].
DERIJARD, B ;
HIBI, M ;
WU, IH ;
BARRETT, T ;
SU, B ;
DENG, TL ;
KARIN, M ;
DAVIS, RJ .
CELL, 1994, 76 (06) :1025-1037
[10]   INDEPENDENT HUMAN MAP KINASE SIGNAL-TRANSDUCTION PATHWAYS DEFINED BY MEK AND MKK ISOFORMS [J].
DERIJARD, B ;
RAINGEAUD, J ;
BARRETT, T ;
WU, IH ;
HAN, JH ;
ULEVITCH, RJ ;
DAVIS, RJ .
SCIENCE, 1995, 267 (5198) :682-685