title: Suppression of EGFR autophosphorylation by FKBP12.
abstract: FK506 binding proteins (FKBPs) represent a subfamily of peptidyl prolyl cis/trans isomerases that can control receptor-mediated intracellular signaling. The prototypic PPIase FKBP12 functionally interacts with EGFR. FKBP12 was shown to inhibit EGF-induced EGFR autophosphorylation with all internal phosphorylation sites equally affected. The inhibition of EGFR catalytic activity is conducted by targeting the EGFR kinase domain. The change of intracellular FKBP12 levels resulted in a change of EGFR autophosphorylation level. Collectively, our results demonstrate that FKBP12 forms an endogenous inhibitor of EGFR phosphorylation directly involved in the control of cellular EGFR activity.
authors: Max Planck Research Unit for Enzymology of Protein Folding, Weinbergweg 22, 06120 Halle (Saale), Germany.
authors: Sebastian
authors: S
authors: Mathea
authors: Sen
authors: S
authors: Li
authors: Angelika
authors: A
authors: Schierhorn
authors: Günther
authors: G
authors: Jahreis
authors: Cordelia
authors: C
authors: Schiene-Fischer
mesh_terms: D045163:Antibodies, Phospho-Specific; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D003432:Cross-Linking Reagents; D019281:Dimerization; D015536:Down-Regulation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D021381:Protein Transport; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction; D022061:Tacrolimus Binding Protein 1A / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D045163:Antibodies, Phospho-Specific; D003432:Cross-Linking Reagents; D009363:Neoplasm Proteins; D047428:Protein Kinase Inhibitors; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D004815:Epidermal Growth Factor; C512478:EGFR protein, human; D066246:ErbB Receptors; D022061:Tacrolimus Binding Protein 1A