Dissecting the EphA3/ephrin-A5 interactions using a novel functional mutagenesis screen

Smith, F. M., Vearing, C., Lackmann, M., Treutlein, H., Himanen, J., Chen, K., Saul, A., Nikolov, D. and Boyd, A. W. (2004) Dissecting the EphA3/ephrin-A5 interactions using a novel functional mutagenesis screen. Journal of Biological Chemistry, 279 10: 9522-9531. doi:10.1074/jbc.M309326200

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Author Smith, F. M.
Vearing, C.
Lackmann, M.
Treutlein, H.
Himanen, J.
Chen, K.
Saul, A.
Nikolov, D.
Boyd, A. W.
Title Dissecting the EphA3/ephrin-A5 interactions using a novel functional mutagenesis screen
Journal name Journal of Biological Chemistry   Check publisher's open access policy
ISSN 0021-9258
Publication date 2004-01-01
Sub-type Article (original research)
DOI 10.1074/jbc.M309326200
Open Access Status File (Publisher version)
Volume 279
Issue 10
Start page 9522
End page 9531
Total pages 10
Editor H. Tabor
Place of publication Bethesda, U.S.A.
Publisher American Society for Biochemistry and Molecular Biology
Language eng
Subject C1
321015 Oncology and Carcinogenesis
320305 Medical Biochemistry - Proteins and Peptides
730108 Cancer and related disorders
Abstract The EphA3 receptor tyrosine kinase preferentially binds ephrin-A5, a member of the corresponding subfamily of membrane-associated ligands. Their interaction regulates critical cell communication functions in normal development and may play a role in neoplasia. Here we describe a random mutagenesis approach, which we employed to study the molecular determinants of the EphA3/ephrin-A5 recognition. Selection and functional characterization of EphA3 point mutants with impaired ephrin-A5 binding from a yeast expression library defined three EphA3 surface areas that are essential for the EphA3/ephrin-A5 interaction. Two of these map to regions identified previously in the crystal structure of the homologous EphB2-ephrin-B2 complex as potential ligand/receptor interfaces. In addition, we identify a third EphA3/ephrin-A5 interface that falls outside the structurally characterized interaction domains. Functional analysis of EphA3 mutants reveals that all three Eph/ephrin contact areas are essential for the assembly of signaling-competent, oligomeric receptor-ligand complexes.
Keyword Biochemistry & Molecular Biology
Receptor Tyrosine Kinase
Eph Receptors
Ligand-binding
Crystal-structure
Hek
Dimerization
Attachment
Ephrins
Domain
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
2005 Higher Education Research Data Collection
School of Medicine Publications
 
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Created: Wed, 15 Aug 2007, 13:22:08 EST