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Possible involvement of pertussis toxin‐sensitive G protein in hepatocyte growth factor‐induced signal transduction in cultured rat hepatocytes: Pertussis toxin treatment inhibits activation of phospholipid signaling, calcium oscillation, and mitogen‐activated protein kinase
Author(s) -
Adachi T,
Nakashima S,
Saji S,
Nakamura T,
Nozawa Y
Publication year - 1997
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.510260207
Subject(s) - pertussis toxin , hepatocyte growth factor , signal transduction , phospholipase c , g protein , biology , hepatocyte , arachidonic acid , kinase , cytosol , protein kinase c , biochemistry , dna synthesis , protein kinase a , microbiology and biotechnology , chemistry , receptor , enzyme , dna , in vitro
Treatment of primary cultured rat hepatocytes with hepatocyte growth factor (HGF) gives rise to inositol phosphate formation, cytosolic calcium oscillation, activation of mitogen‐activated protein (MAP) kinase and phospholipase D (PLD), and arachidonic acid release, leading to DNA synthesis. Pretreatment of cultured hepatocytes with pertussis toxin (PT), which is known to adenosine diphosphate‐ribosylate Gi and Go guanine nucleotide ‐binding proteins and to inhibit their functions, partially inhibited HGF‐induced [3H]thymidine incorporation in a concentration‐dependent manner. These results suggest that HGF‐mediated DNA synthesis of hepatocytes is partly regulated via PT‐sensitive guanine nucleotide‐binding protein. Therefore, the effects of PT treatment on HGF‐induced signal‐transduction pathways were investigated. HGF‐induced MAP kinase activation and arachidonic acid release were decreased by PT treatment, whereas PLD activation was diminished by PT to the level of unstimulated control. PT also interfered with HGF‐induced inositol phosphate formation and cytosolic calcium oscillation. These results suggest that both PT‐sensitive and PT‐insensitive pathways are involved in HGF‐induced signaling.