Epidermal growth factor receptor potentiates MCM7-mediated DNA replication through tyrosine phosphorylation of Lyn kinase in human cancers.
Cancer Cell
; 23(6): 796-810, 2013 Jun 10.
Article
em En
| MEDLINE
| ID: mdl-23764002
ABSTRACT
Epidermal growth factor receptor (EGFR) initiates a signaling cascade that leads to DNA synthesis and cell proliferation, but its role in regulating DNA replication licensing is unclear. Here, we show that activated EGFR phosphorylates the p56 isoform of Lyn, p56(Lyn), at Y32, which then phosphorylates MCM7, a licensing factor critical for DNA replication, at Y600 to increase its association with other minichromosome maintenance complex proteins, thereby promoting DNA synthesis complex assembly and cell proliferation. Both p56(Lyn) Y32 and MCM7 Y600 phosphorylation are enhanced in proliferating cells and correlated with poor survival of breast cancer patients. These results establish a signaling cascade in which EGFR enhances MCM7 phosphorylation and DNA replication through Lyn phosphorylation in human cancer cells.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
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Proteínas Nucleares
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Proteínas de Ciclo Celular
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Quinases da Família src
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Proteínas de Ligação a DNA
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Replicação do DNA
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Receptores ErbB
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article