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Effects of pertussis toxin on extracellular signal‐regulated kinase activation in hepatocytes by hormones and receptor‐independent agents: Evidence suggesting a stimulatory role of G i proteins at a level distal to receptor coupling
Author(s) -
Melien Øyvind,
Sandnes Dagny,
Johansen Ellen Johanne,
Christoffersen Thoralf
Publication year - 2000
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(200007)184:1<27::aid-jcp3>3.0.co;2-q
Subject(s) - pertussis toxin , phospholipase c , protein kinase c , biology , receptor , microbiology and biotechnology , signal transduction , mapk/erk pathway , endocrinology , phospholipase d , extracellular , medicine , g protein coupled receptor , g protein , biochemistry
It was previously found that pertussis toxin (PTX) pretreatment inhibits the activation of extracellular signal‐regulated kinases ERK1 (p44 mapk ) and ERK2 (p42 mapk ) in hepatocytes in response to either agonists that bind to heptahelical receptors or epidermal growth factor (EGF), suggesting a role of G i proteins in stimulatory mechanisms for ERK1/2. The present work shows that ERK1/2 is activated in a PTX‐sensitive way not only by vasopressin, angiotensin II, prostaglandin (PG) F 2α , α 1 ‐adrenergic stimulation, and EGF but also by agents whose actions bypass receptors and stimulate protein kinase C (PKC) and/or elevate intracellular Ca 2+ , such as 12‐O‐tetradecanoyl phorbol‐13‐acetate (TPA), exogenous phosphatidylcholine‐specific phospholipase C (PC‐PLC, from Bacillus cereus ), thapsigargin, and the Ca 2+ ionophore A23187. Under the same conditions, PTX did not affect agonist stimulation of phosphoinositide‐specific phospholipase C (PI‐PLC) (IP 3 generation), and did not reduce the activation by these agents of phospholipase D (PLD). The results suggest that in hepatocytes a PTX‐sensitive mechanism, presumably involving G i proteins, exerts a stimulatory effect on ERK at a level distal to receptor coupling, acting either as an integral part of the signaling pathway(s) or by a permissive, synergistic regulation. J. Cell. Physiol. 184:27–36, 2000. © 2000 Wiley‐Liss, Inc.