Kinase activity-independent role of EphA2 in the regulation of M-phase progression.
Exp Cell Res
; 395(2): 112207, 2020 10 15.
Article
en En
| MEDLINE
| ID: mdl-32750331
ABSTRACT
Cell division is a tightly regulated, essential process for cell proliferation. Very recently, we reported that EphA2 is phosphorylated at Ser897, via the Cdk1/MEK/ERK/RSK pathway, during M phase and contributes to proper M-phase progression by maintaining cortical rigidity via the EphA2pSer897/ephexin4/RhoG pathway. Here, we show that EphA2 kinase activity is dispensable for M-phase progression. Although EphA2 knockdown delayed this progression, the delay was rescued by an EphA2 mutant expression with an Asp739 to Asn substitution, as well as by wild-type EphA2. Western blotting analysis confirmed that the Asp739Asn mutant lost its EphA2 kinase activity. Like wild-type EphA2, the Asp739Asn mutant was localized to the plasma membrane irrespective of cell cycle. While RhoG localization to the plasma membrane was decreased in EphA2 knockdown cells, it was rescued by re-expression of wild-type EphA2 but not via the mutant containing the Ser897 to Ala substitution. This confirmed our recent report that phosphorylation at Ser897 is responsible for RhoG localization to the plasma membrane. In agreement with the M-phase progression's rescue effect, the Asp739Asn mutant rescued RhoG localization in EphA2 knockdown cells. These results suggest that EphA2 regulates M-phase progression in a manner independent of its kinase activity.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Ciclo Celular
/
División Celular
/
Efrina-A2
/
Proliferación Celular
Límite:
Humans
Idioma:
En
Revista:
Exp Cell Res
Año:
2020
Tipo del documento:
Article
País de afiliación:
Japón