Titre du document / Document title

A mutation in the common docking domain of ERK2 in a human cancer cell line, which was associated with its constitutive phosphorylation

Auteur(s) / Author(s)

ANARVIND Ramanath ⁽¹⁾ ; SHIMAMOTO Hiroaki ^{(1 2)} ; MOMOSE Fumio ⁽³⁾ ; AMAGASA Teruo ⁽³⁾ ; OMURA Ken ⁽²⁾ ; TSUCHIDA Nobuo ⁽¹⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Department of Molecular Cellular Oncology and Microbiology, Graduate School of Medicine and Dentistry, Tokyo Medical and Dental University, 113-8549 Tokyo, JAPON
⁽²⁾ Department of Oral and Maxillofacial Surgery, Graduate School of Medicine and Dentistry, Tokyo Medical and Dental University, 113-8549 Tokyo, JAPON
⁽³⁾ Department of Maxillofacial Surgery, Graduate School of Medicine and Dentistry, Tokyo Medical and Dental University, 113-8549 Tokyo, JAPON

Résumé / Abstract

The EGFR/Ras/Raf/MEK/ERK pathway is a major pathway involved in the control of growth signals, cell survival and differentiation. Mutations of signaling components, such as EGFR (c-erbBI), Ras, and B-Raf, have been shown to play roles in the genesis of human cancer, while point mutation of ERK has not been reported. In this study, we present evidence for a mutation in an oral squamous cell carcinoma cell line, HSC6. PCR-amplification of cDNA, cloning and sequencing resulted in the identification of glutamic acid to lysine substitution at codon 322 (E322K) that occurred in the common docking (CD) domain of ERK2. The mutant protein contributed towards faster-migration in SDS-PAGE, and constitutive phosphorylation in a MEK-dependent manner. The transient transfection of the mutant ERK2 in 293T cells resulted in the expression of the same faster-migrating band in SDS-PAGE as was detected in HSC6 cells, which was preferentially phosphorylated relative to endogenous wild-type ERK2. The present study is the first to report ERK2 substitution mutation in a human cancer cell line which resulted in constitutive phosphorylation.

Revue / Journal Title

International journal of oncology   ISSN 1019-6439 

Source / Source

2005, vol. 27, n^o6, pp. 1499-1504 [6 page(s) (article)] (33 ref.)

Langue / Language

Anglais

Editeur / Publisher

Editorial Academy of the International Journal of Oncology, Athens, GRECE  (1992) (Revue)

Mots-clés anglais / English Keywords

Enzyme ; Extracellular signal-regulated protein kinase 2 ; Cancerology ; Signal transduction ; Phosphorylation ; Established cell line ; Tumor cell ; Human ; Mitogen-activated protein kinase ; Squamous cell carcinoma ; Genetics ; Mutation ; Malignant tumor ;

Mots-clés français / French Keywords

Enzyme ; Extracellular signal-regulated protein kinase 2 ; Cancérologie ; Transduction signal ; Phosphorylation ; Lignée cellulaire établie ; Cellule tumorale ; Homme ; Mitogen-activated protein kinase ; Carcinome épidermoïde ; Génétique ; Mutation ; Tumeur maligne ;

Mots-clés espagnols / Spanish Keywords

Enzima ; Cancerología ; Transducción señal ; Fosforilación ; Línea celular establecida ; Célula tumoral ; Hombre ; Mitogen-activated protein kinase ; Carcinoma epidermoide ; Genética ; Mutación ; Tumor maligno ;

Mots-clés d'auteur / Author Keywords

ERK2 ; mutation ; common docking domain ; squamous cell carcinoma ; signal transduction ; sevenmaker ;

Localisation / Location

INIST-CNRS, Cote INIST : 26333, 35400013570206.0040