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rho‐mediated protein tyrosine phosphorylation in lysophosphatidic‐acid‐induced tumor‐cell invasion
Author(s) -
Imamura Fumio,
Shinkai Kiyoko,
Mukai Mutsuko,
Yoshioka Kiyoko,
Komagome Rika,
Iwasaki Teruo,
Akedo Hitoshi
Publication year - 1996
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19960301)65:5<627::aid-ijc12>3.0.co;2-4
Subject(s) - lysophosphatidic acid , tyrosine phosphorylation , phosphorylation , biology , tyrosine , genistein , tyrosine kinase , tyrosine kinase inhibitor , protein tyrosine phosphatase , paxillin , microbiology and biotechnology , ptk2 , platelet derived growth factor receptor , focal adhesion , cancer research , signal transduction , protein kinase a , biochemistry , endocrinology , growth factor , mitogen activated protein kinase kinase , cancer , genetics , receptor
Rat ascites hepatoma cells (MMI) invade a mesothelial cell monolayer in vitro in assay medium containing serum, but not in serum‐free medium. Serum could be completely replaced by I‐oleoyl lysophosphatidic acid (LPA) in inducing invasion. LPA‐induced invasion was inhibited by genistein, a tyrosine‐kinase inhibitor. Protein tyrosine phosphorylation in response to LPA was thus analyzed in order to determine the molecular mechanism of invasion. LPA of invasion‐inducible concentrations evoked a transient increase in tyrosine phosphorylation, mainly of 110‐ to 130‐kDa proteins in MMI cells but not in mesothelial cells. These concentrations of LPA were over 10 times higher (10 to 25 μM) than those necessary to produce a variety of biological actions, such as tyrosine phosphorylation in fibroblasts, neurite retraction and platelet aggregation. Protein tyrosine phosphorylation and invasion by MMI cells induced by LPA are largely regulated by rho p21, because both were inhibited by Clostridium botulinum C3 exo‐enzyme, which is known to specifically inactivate rho p21. Invasion of MCL by MMI cells induced by serum and that by B16FE7 cells induced by LPA were inhibited by genistein or C3 as well. By immunoprecipitation, we detected p125 focal adhesion kinase (FAK) as a major protein of 110‐ to 130‐kDa tyrosine phosphorylated in response to LPA. Tyrosine phosphorylation of paxillin by LPA was also detected. © 1996 Wiley‐Liss, Inc.