Premium
Activation of p42/p44 mitogen‐activated protein kinase by angiotensin II, vasopressin, norepinephrine, and prostaglandin F 2α in hepatocytes is sustained, and like the effect of epidermal growth factor, mediated through pertussis toxin‐sensitive mechanisms
Author(s) -
Melien Øyvind,
Thoresen G. Hege,
Sandnes Dagny,
Østby Eva,
Christoffersen Thoralf
Publication year - 1998
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(199806)175:3<348::aid-jcp13>3.0.co;2-1
Subject(s) - endocrinology , medicine , pertussis toxin , protein kinase a , protein kinase c , phospholipase c , biology , angiotensin ii , signal transduction , epidermal growth factor , kinase , chemistry , g protein , receptor , microbiology and biotechnology , blood pressure
Several agents that act through G‐protein‐coupled receptors and also stimulate phosphoinositide‐specific phospholipase C (PI‐PLC), including angiotensin II, vasopressin, norepinephrine, and prostaglandin (PG) F 2α , activated the ERK1 (p44 mapk ) and ERK2 (p42 mapk ) members of the mitogen‐activated protein (MAP) kinase family in primary cultures of rat hepatocytes, measured as phosphorylation of myelin basic protein (MBP) by a partially purified enzyme, immunoblotting, and in‐gel assays. All these agonists induced a peak activation (two to threefold increase in MBP‐phosphorylation) at 3–5 min, followed by a brief decrease, and then a sustained elevation or a second increase of the MAP kinase activity that lasted for several hours. Although all the above agents also stimulated PI‐PLC, implicating a G q ‐dependent pathway, the elevations of the concentration of inositol (1,4,5)‐trisphosphate did not correlate well with the MAP kinase activity. Furthermore, pretreatment of the cells with pertussis toxin markedly reduced the MAP kinase activation by angiotensin II, vasopressin, norepinephrine, or PGF 2α . In addition, hepatocytes pretreated with pertussis toxin showed a diminished MAP kinase response to epidermal growth factor (EGF). The results indicate that agonists acting via G‐protein‐coupled receptors have the ability to induce sustained activation of MAP kinase in hepatocytes, and suggest that G i ‐dependent mechanisms are required for full activation of the MAP kinase signal transduction pathway by G‐protein‐coupled receptors as well as the EGF receptor. J. Cell. Physiol. 175:348–358, 1998. © 1998 Wiley‐Liss, Inc.