Universität zu Köln

Bill, Anke, Schmitz, Anton, Albertoni, Barbara, Song, Jin-Na, Heukamp, Lukas C., Walrafen, David, Thorwirth, Franziska, Verveer, Peter J., Zimmer, Sebastian, Meffert, Lisa, Schreiber, Arne, Chatterjee, Sampurna, Thomas, Roman K., Ullrich, Roland T., Lang, Thorsten and Famulok, Michael (2010). RETRACTED: Cytohesins Are Cytoplasmic ErbB Receptor Activators (Retracted article. See vol. 165, pg. 1293, 2016). Cell, 143 (2). S. 201 - 212. CAMBRIDGE: CELL PRESS. ISSN 1097-4172

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Abstract

Signaling by ErbB receptors requires the activation of their cytoplasmic kinase domains, which is initiated by ligand binding to the receptor ectodomains. Cytoplasmic factors contributing to the activation are unknown. Here we identify members of the cytohesin protein family as such factors. Cytohesin inhibition decreased ErbB receptor autophosphorylation and signaling, whereas cytohesin overexpression stimulated receptor activation. Monitoring epidermal growth factor receptor (EGFR) conformation by anisotropy microscopy together with cell-free reconstitution of cytohesin-dependent receptor autophosphorylation indicate that cytohesins facilitate conformational rearrangements in the intracellular domains of dimerized receptors. Consistent with cytohesins playing a prominent role in ErbB receptor signaling, we found that cytohesin overexpression correlated with EGF signaling pathway activation in human lung adenocarcinomas. Chemical inhibition of cytohesins resulted in reduced proliferation of EGFR-dependent lung cancer cells in vitro and in vivo. Our results establish cytohesins as cytoplasmic conformational activators of ErbB receptors that are of pathophysiological relevance.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Bill, Anke UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmitz, Anton UNSPECIFIED UNSPECIFIED UNSPECIFIED Albertoni, Barbara UNSPECIFIED UNSPECIFIED UNSPECIFIED Song, Jin-Na UNSPECIFIED UNSPECIFIED UNSPECIFIED Heukamp, Lukas C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Walrafen, David UNSPECIFIED UNSPECIFIED UNSPECIFIED Thorwirth, Franziska UNSPECIFIED UNSPECIFIED UNSPECIFIED Verveer, Peter J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Zimmer, Sebastian UNSPECIFIED UNSPECIFIED UNSPECIFIED Meffert, Lisa UNSPECIFIED UNSPECIFIED UNSPECIFIED Schreiber, Arne UNSPECIFIED UNSPECIFIED UNSPECIFIED Chatterjee, Sampurna UNSPECIFIED UNSPECIFIED UNSPECIFIED Thomas, Roman K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ullrich, Roland T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lang, Thorsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Famulok, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-494238
DOI:	10.1016/j.cell.2010.09.011
Journal or Publication Title:	Cell
Volume:	143
Number:	2
Page Range:	S. 201 - 212
Date:	2010
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	1097-4172
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GROWTH-FACTOR RECEPTOR; CELL LUNG-CANCER; EGF RECEPTOR; KINASE DOMAIN; CLINICAL-RESPONSE; MUTATIONS; DIMERIZATION; INHIBITION; MECHANISM; FAMILY Multiple languages Biochemistry & Molecular Biology; Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/49423