Effects of pertussis toxin on extracellular signal-regulated kinase activation in hepatocytes by hormones and receptor-independent agents: Evidence suggesting a stimulatory role of Gi proteins at a level distal to receptor coupling
✍ Scribed by Øyvind Melien; Dagny Sandnes; Ellen Johanne Johansen; Thoralf Christoffersen
- Publisher
- John Wiley and Sons
- Year
- 2000
- Tongue
- English
- Weight
- 242 KB
- Volume
- 184
- Category
- Article
- ISSN
- 0021-9541
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✦ Synopsis
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 2␣ , ␣ 1 -adrenergic stimulation, and EGF but also by agents whose actions bypass receptors and stimulate protein kinase C (PKC) and/or elevate intracellular Ca 2ϩ , such as 12-O-tetradecanoyl phorbol-13-acetate (TPA), exogenous phosphatidylcholine-specific phospholipase C (PC-PLC, from Bacillus cereus), thapsigargin, and the Ca 2ϩ ionophore A23187. Under the same condi- tions, 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.