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p38 Is a Key Signaling Molecule for H‐ ras ‐Induced Inhibition of Gap Junction Intercellular Communication in Rat Liver Epithelial Cells
Author(s) -
LEE KI WON,
JUNG JI WON,
KANG KYUNGSUN,
LEE HYONG JOO
Publication year - 2004
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1329.032
Subject(s) - microbiology and biotechnology , p38 mitogen activated protein kinases , kinase , mapk/erk pathway , intracellular , connexin , cell signaling , signal transduction , chemistry , gap junction , protein kinase a , extracellular , hydrogen peroxide , biology , biochemistry
A bstract : Multiple lines of evidence indicate that inhibition of gap junction intercellular communication (GJIC) is a major carcinogenic process. Several reports suggest that activation of extracellular signal‐regulated protein kinases 1 and 2 (ERK1/2) plays a key role in the disrupted GJIC by hydrogen peroxide, 12‐ O ‐tetradecanoylphorbol‐13‐acetate, and quinones in rat liver epithelial cells. Recently, we reported that p38 mitogen‐activated protein kinase (MAPK) is also involved in the inhibition of GJIC by hydrogen peroxide in WB‐F344 rat liver epithelial cells (WB cells). The present study investigated the role of ERK1/2 and p38 MAPK in H‐ ras ‐induced inhibition of GJIC in WB cells. H‐ ras induces complete inhibition of GJIC and unphosphorylation of connexin 43 (Cx43) in WB cells. SB203580, an inhibitor of p38, restored inhibition of GJIC and blocked unphosphorylation of Cx43 in H‐ ras ‐transformed WB cells. However, PD98059, an inhibitor of ERK1/2, had no effect. Our results suggest that the disruption of GJIC induced by H‐ ras may be strongly related to the unphosphorylation of Cx43 via the activation of p38 but not ERK1/2. Thus, p38 is a key signaling molecule for H‐ ras ‐induced inhibition of GJIC in WB cells.