Dissecting the EphA3/Ephrin-A5 interactions using a novel functional mutagenesis screen.
J Biol Chem
; 279(10): 9522-31, 2004 Mar 05.
Article
em En
| MEDLINE
| ID: mdl-14660665
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.
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Base de dados:
MEDLINE
Assunto principal:
Receptores Proteína Tirosina Quinases
/
Mapeamento de Interação de Proteínas
/
Efrina-A5
Limite:
Humans
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
2004
Tipo de documento:
Article
País de afiliação:
Austrália