ACTIVATION OF THE STAT PATHWAY BY ANGIOTENSIN-II IN T3CHO/AT(1A) CELLS - CROSS-TALK BETWEEN ANGIOTENSIN-II AND INTERLEUKIN-6 NUCLEAR SIGNALING

被引:73
作者
BHAT, GJ
THEKKUMKARA, TJ
THOMAS, WG
CONRAD, KM
BAKER, KM
机构
[1] Weis Center for Research, Danville, PA 17822
关键词
D O I
10.1074/jbc.270.32.19059
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
We recently reported that angiotensin II (AII), acting through the STAT (Signal Transducers and Activators of Transcription) pathway, stimulated a delayed SIF (sis-inducing factor)-like DNA binding activity (maximal at 2-3 h) (Bhat, G. J., Thekkumkara, T. J., Thomas, W. G., Conrad, K. M., and Baker, K. M. (1994) J. Biol. Chem. 269, 31443-31449). Using a cell line transfected with the AT(1A) receptor (T3CHO/AT(1A)), we further characterized the AII-induced SIF response and explored the possible rea sons for the delay in stimulated SIF activity, In cells transfected with a chloramphenicol acetyltransferase reporter plasmid, under the control of a SIE (sis-inducing element), AII markedly stimulated chloramphenicol acetyltransferase activity. The delayed SIF activation by AII was not due to a requirement for the release of other SIF inducing factors into the medium and contrasts with the rapid (5 min) induction elicited by the cytokine, interleukin-6 (IL-6), Interestingly, both agents stimulated tyrosine phosphorylation of Stat92 and predominantly the formation of SIF complex A. We tested the hypothesis that AII initially activated an inhibitory pathway, which was responsible for delaying the maximal SIF stimulation until 2 h, Pretreatment of cells for 15 min with AII resulted in significant inhibition of the IL-6-induced nuclear SIF response (10 min) and Stat92 tyrosine phosphorylation, which was blocked by EXP3174, an AT(1) receptor antagonist. This inhibition was transient with return of the IL-6-induced SIF response at 2 h, suggesting that the delayed maximal activation of SIF by AII occurs following an initial transient inhibitory phase, Pretreatment of cells with phorbol 12-myristate 13-acetate for 15 min, to activate protein kinase C, resulted in inhibition of the IL-6-induced SIF response (10 min). However, down-regulation of protein kinase C activity prevented phorbol 12-myristate 13-acetate, but not AII mediated inhibition of the IL-6-induced SIF response. Although the mechanism is not clear, the results presented in this paper raise the interesting possibility that the activation of SIF/Stat92 by AII is characterized by an initial inhibitory phase, followed by the induction process. The observation that AII and IL-6 utilize similar components of the STAT pathway and that AII can cross-talk with IL-6 signaling through inhibition of IL-6-induced SIF/Stat92, implies a modulatory role for AII in cellular responses to cytokines.
引用
收藏
页码:19059 / 19065
页数:7
相关论文
共 47 条
[1]   [SAR1]ANGIOTENSIN-2 RECEPTOR-MEDIATED STIMULATION OF PROTEIN-SYNTHESIS IN CHICK HEART-CELLS [J].
ACETO, JF ;
BAKER, KM .
AMERICAN JOURNAL OF PHYSIOLOGY, 1990, 258 (03) :H806-H813
[2]   MOLECULAR-CLONING OF APRF, A NOVEL IFN-STIMULATED GENE FACTOR-3 P91-RELATED TRANSCRIPTION FACTOR INVOLVED IN THE GP130-MEDIATED SIGNALING PATHWAY [J].
AKIRA, S ;
NISHIO, Y ;
INOUE, M ;
WANG, XJ ;
WEI, S ;
MATSUSAKA, T ;
YOSHIDA, K ;
SUDO, T ;
NARUTO, M ;
KISHIMOTO, T .
CELL, 1994, 77 (01) :63-71
[3]   ANGIOTENSIN-II-STIMULATED PROTEIN-SYNTHESIS IN CULTURED VASCULAR SMOOTH-MUSCLE CELLS [J].
BERK, BC ;
VEKSHTEIN, V ;
GORDON, HM ;
TSUDA, T .
HYPERTENSION, 1989, 13 (04) :305-314
[4]  
BHAT GJ, 1994, J BIOL CHEM, V269, P31443
[5]   INVOLVEMENT OF PROTEIN-KINASE-C AND CA2+ IN ANGIOTENSIN-II-INDUCED MITOGENESIS OF CARDIAC FIBROBLASTS [J].
BOOZ, GW ;
DOSTAL, DE ;
SINGER, HA ;
BAKER, KM .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 1994, 267 (05) :C1308-C1318
[6]  
BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3
[7]  
CRABB DW, 1989, METHOD ENZYMOL, V168, P690
[8]   CHARACTERIZATION OF ANGIOTENSIN-II RECEPTORS IN CULTURED ADULT-RAT CARDIAC FIBROBLASTS - COUPLING TO SIGNALING SYSTEMS AND GENE-EXPRESSION [J].
CRABOS, M ;
ROTH, M ;
HAHN, AWA ;
ERNE, P .
JOURNAL OF CLINICAL INVESTIGATION, 1994, 93 (06) :2372-2378
[9]   ANGIOTENSIN-II INDUCES FIBRONECTIN EXPRESSION ASSOCIATED WITH CARDIAC FIBROSIS IN THE RAT [J].
CRAWFORD, DC ;
CHOBANIAN, AV ;
BRECHER, P .
CIRCULATION RESEARCH, 1994, 74 (04) :727-739
[10]   JAK-STAT PATHWAYS AND TRANSCRIPTIONAL ACTIVATION IN RESPONSE TO IFNS AND OTHER EXTRACELLULAR SIGNALING PROTEINS [J].
DARNELL, JE ;
KERR, IM ;
STARK, GR .
SCIENCE, 1994, 264 (5164) :1415-1421