title: Differential activation of ERKs to focal adhesions by PKC epsilon is required for PMA-induced adhesion and migration of human glioma cells.
abstract: Protein kinase C (PKC) is a family of serine/threonine kinases involved in the transduction of a variety of signals. There is increasing evidence to indicate that specific PKC isoforms are involved in the regulation of distinct cellular processes. In glioma cells, PKC alpha was found to be a critical regulator of proliferation and cell cycle progression, while PKC epsilon was found to regulate adhesion and migration. Herein, we report that specific PKC isoforms are able to differentially activate extracellular-signal regulated kinase (ERK) in distinct cellular locations: while PKC alpha induces the activation of nuclear ERK, PKC epsilon induces the activation of ERK at focal adhesions. Inhibition of the ERK pathway completely abolished the PKC-induced integrin-mediated adhesion and migration. Thus, we present the first evidence that PKC epsilon is able to activate ERK at focal adhesions to mediate glioma cell adhesion and motility, providing a molecular mechanism to explain the different biological functions of PKC alpha and epsilon in glioma cells.
authors.affiliation: Department of Oncology, University of Calgary, Calgary, Alberta, T2N 4N1, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Besson
authors.forename: A
authors.initials: A
authors.lastname: Davy
authors.forename: S M
authors.initials: SM
authors.lastname: Robbins
authors.forename: V W
authors.initials: VW
authors.lastname: Yong
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D001932:Brain Neoplasms / Q000201:enzymology / Q000473:pathology*; D002070:Butadienes / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D022001:Focal Adhesions / Q000502:physiology*; D005910:Glioma / Q000201:enzymology / Q000473:pathology*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D051744:Protein Kinase C-epsilon; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D000077191:Wortmannin
chemical_list: C412373:AG 1879; D000730:Androstadienes; D002070:Butadienes; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D009363:Neoplasm Proteins; D009570:Nitriles; D011743:Pyrimidines; C113580:U 0126; C482128:MAP2K2 protein, human; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; C497255:PRKCE protein, human; D011493:Protein Kinase C; D051744:Protein Kinase C-epsilon; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; C482125:MAP2K1 protein, human; D020929:Mitogen-Activated Protein Kinase Kinases; D013755:Tetradecanoylphorbol Acetate; D000077191:Wortmannin