Angiotensin II induces diverse signal transduction pathways via both Gq and Gi proteins in liver epithelial cells.
Angiotensin II stimulates a biphasic activation of Raf-1, MEK, and ERK in WB liver epithelial cells. The first peak of activity is rapid and transient and is followed by a sustained phase. Angiotensin II also causes a rapid activation of p21ras in these cells. Moreover, two Src family kinases (Fyn and Yes) were activated by angiotensin II in a time- and concentration-dependent manner. Microinjection of antibodies against Fyn and Yes blocked angiotensin II-induced DNA synthesis and c-Fos expression in WB cells, indicating an obligatory involvement of these tyrosine kinases in the activation of the ERK cascade by angiotensin II. Finally, substantial reduction of the angiotensin II-stimulated activation of Fyn, Raf-1, ERK, and expression of c-Fos by pertussis toxin pretreatment argues that G proteins of the Gi family as well as the Gq family are involved in angiotensin II-mediated mitogenic pathways in WB cells.
Tsygankova
O M
OM
Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Peng
M
M
Maloney
J A
JA
Hopkins
N
N
Williamson
J R
JR
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D048369:MAP Kinase Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051076:Proto-Oncogene Proteins c-fyn; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D051575:Proto-Oncogene Proteins c-yes; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D019061:src-Family Kinases
D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D000804:Angiotensin II; D011505:Protein-Tyrosine Kinases; C494961:Fyn protein, rat; D051076:Proto-Oncogene Proteins c-fyn; D051575:Proto-Oncogene Proteins c-yes; D019061:src-Family Kinases; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf; D048369:MAP Kinase Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases; D019204:GTP-Binding Proteins