Extracellular signal-regulated kinase and the small GTP-binding protein p21Rac1 are involved in the regulation of gene transcription by angiotensin II.
To study the role of extracellular-signal-regulated kinase (ERK) cascade and the small GTP-ase proteins in the activation of the c-fos promoter by angiotensin II (AII), transient transfection experiments were performed in CHO cells stably expressing the rat AT(1A) receptor. In this system AII activated ERK in 1 min and also increased the transcriptional activity of the c-fos promoter-luciferase reporter gene construct. The activation of the promoter proved to be dependent on the Ras-Raf-ERK cascade as cotransfection of expression vectors known to specifically inhibit this cascade blocked the effect of AII. Dominant-negative p21Rac1 mutant partially blocked the activation of the c-fos promoter by AII. However, activation of the c-fos promoter was independent of protein kinase C (PKC) as bisindolylmaleimide I, a specific PKC inhibitor did not block the effect of AII. These results suggest that AII activates the transcription of the c-fos through the Ras-Raf-ERK cascade. Furthermore, p21Rac1 is involved in the modulation of the c-fos promoter by AII.
Huszár
T
T
Department of Pathophysiology, Faculty of Medicine, International Nephrology Training and Research Center, Semmelweis University, Budapest, Hungary.
Mucsi
I
I
Antus
B
B
Terebessy
T
T
Jeney
C
C
Masszi
A
A
Hunyady
L
L
Mihalik
B
B
Goldberg
H J
HJ
Thekkumkara
T J
TJ
Rosivall
L
L
D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D019908:Proto-Oncogene Proteins c-raf / Q000502:physiology; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000502:physiology; D014158:Transcription, Genetic / Q000502:physiology*; D020830:rac1 GTP-Binding Protein / Q000502:physiology*; D018631:ras Proteins / Q000502:physiology
D016760:Proto-Oncogene Proteins c-fos; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D019869:Phosphatidylinositol 3-Kinases; D019908:Proto-Oncogene Proteins c-raf; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D020830:rac1 GTP-Binding Protein; D018631:ras Proteins