Suppression of EGFR Autophosphorylation by FKBP12

• Published in: Biochemistry (Easton) Vol. 50; no. 50; pp. 10844 - 10850
• Main Authors: Mathea, Sebastian, Li, Sen, Schierhorn, Angelika, Jahreis, Günther, Schiene-Fischer, Cordelia
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 20.12.2011
• Subjects: Antibodies, Phospho-Specific; Carcinoma - metabolism; Carcinoma - pathology; Cell Line, Tumor; Cross-Linking Reagents; Dimerization; Down-Regulation - drug effects; Epidermal Growth Factor - metabolism; Gene Silencing; HeLa Cells; Humans; Kinetics; Neoplasm Proteins - antagonists & inhibitors; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Phosphorylation - drug effects; Protein Kinase Inhibitors - pharmacology; Protein Transport; Receptor, Epidermal Growth Factor - antagonists & inhibitors; Receptor, Epidermal Growth Factor - genetics; Receptor, Epidermal Growth Factor - metabolism; Recombinant Fusion Proteins - antagonists & inhibitors; Recombinant Fusion Proteins - metabolism; Recombinant Proteins - antagonists & inhibitors; Recombinant Proteins - metabolism; RNA, Small Interfering; Signal Transduction; Tacrolimus Binding Protein 1A - antagonists & inhibitors; Tacrolimus Binding Protein 1A - genetics; Tacrolimus Binding Protein 1A - metabolism
• ISSN: 0006-2960; 1520-4995
• DOI: 10.1021/bi2013855

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.