title: Role of calmodulin in the modulation of the MAPK signalling pathway and the transactivation of epidermal growth factor receptor mediated by PKC.
abstract: We have recently shown that calmodulin (CaM) regulates the trafficking of epidermal growth factor receptor (EGFR) as well as the mitogen-activated protein kinase (MAPK) signalling pathway. However, the overall regulation of the MAPK pathway is achieved through a complex interplay of other several upstream effectors including G-proteins, EGF, EGFR, protein kinase C (PKC), phosphatidylinositol-3-kinase and CaM. In order to understand the role of CaM in the PKC-mediated transactivation of EGFR we have analysed the effect of a CaM antagonist, N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide, on the 12-O-tetradecanoylphorbol-13-acetate-mediated activation of EGFR and the subsequent MAPK activation. The results show that CaM interferes with MAPK activation and the transactivation of EGFR mediated by PKC.
authors.affiliation: Departament de Biologia Cellular, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Francesc
authors.initials: F
authors.lastname: Tebar
authors.forename: Anna
authors.initials: A
authors.lastname: Lladó
authors.forename: Carlos
authors.initials: C
authors.lastname: Enrich
mesh_terms: D000818:Animals; D019556:COS Cells / Q000378:metabolism; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002522:Chlorocebus aethiops; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology*; D011799:Quinazolines; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013449:Sulfonamides / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology; D015533:Transcriptional Activation / Q000187:drug effects / Q000502:physiology*; D020032:Tyrphostins / Q000494:pharmacology; D018631:ras Proteins / Q000378:metabolism
chemical_list: D002147:Calmodulin; D004791:Enzyme Inhibitors; D011799:Quinazolines; D013449:Sulfonamides; D013876:Thiophenes; D020032:Tyrphostins; C101044:RTKI cpd; D010649:Phenylalanine; C033772:N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide; C080985:batimastat; D066246:ErbB Receptors; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D018631:ras Proteins; D013755:Tetradecanoylphorbol Acetate