Protein kinase cascade activated by mechanical stress in cardiocytes: possible involvement of angiotensin II.
Mechanical stress induces cardiac hypertrophy and expression of specific genes in the cardiac myocytes. External stimuli are generally transduced into the nucleus through the activation of a protein kinase cascade. We have previously shown that stretching cardiomyocytes stimulates the activity of protein kinase C (PKC), mitogen-activated protein (MAP) kinase and S6 protein kinase. In the present study, we examined two other kinases, Raf-1 kinase and MAP kinase kinase, which are supposed to lie between PKC and MAP kinase in the protein kinase cascade. Stretching cardiocytes by using the in vitro system induced hyperphosphorylation of Raf-1 kinase and activation of MAP kinase kinase. The protein kinases activated by mechanical stress are similar to those activated by growth factors. We examined the possible involvement of angiotensin II (Ang II) in the protein synthesis and gene expression induced by mechanical stress. CV11974, an Ang II-receptor antagonist, partially suppressed the increases in amino acid incorporation, c-fos gene expression and MAP kinase activity induced by stretching. These results suggest that a variety of protein kinases are activated by mechanical stress and that locally produced Ang II may in part play important roles in converting mechanical stimuli into biochemical signals.
Komuro
I
I
Department of Medicine III, University of Tokyo, Japan.
Yamazaki
T
T
Katoh
Y
Y
Tobe
K
K
Kadowaki
T
T
Nagai
R
R
Yazaki
Y
Y
D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D015870:Gene Expression / Q000187:drug effects; D020929:Mitogen-Activated Protein Kinase Kinases; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D019908:Proto-Oncogene Proteins c-raf; D051381:Rats; D017208:Rats, Wistar; D013314:Stress, Mechanical; D013777:Tetrazoles / Q000494:pharmacology
D001562:Benzimidazoles; D001713:Biphenyl Compounds; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D013777:Tetrazoles; D000804:Angiotensin II; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf; D020929:Mitogen-Activated Protein Kinase Kinases; C081643:candesartan