Kinase activity-independent role of EphA2 in the regulation of M-phase progression.
CDC2 Protein Kinase
/ metabolism
Cell Cycle
/ physiology
Cell Division
/ physiology
Cell Proliferation
/ physiology
Ephrin-A2
/ metabolism
Guanine Nucleotide Exchange Factors
/ metabolism
HeLa Cells
Humans
MAP Kinase Signaling System
/ physiology
Phosphoserine
/ metabolism
Receptor, EphA2
Signal Transduction
/ physiology
EphA2
Kinase
M phase
Phosphorylation
RO-3306
Journal
Experimental cell research
ISSN: 1090-2422
Titre abrégé: Exp Cell Res
Pays: United States
ID NLM: 0373226
Informations de publication
Date de publication:
15 10 2020
15 10 2020
Historique:
received:
14
08
2019
revised:
17
07
2020
accepted:
26
07
2020
pubmed:
5
8
2020
medline:
4
3
2021
entrez:
5
8
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32750331
pii: S0014-4827(20)30456-0
doi: 10.1016/j.yexcr.2020.112207
pii:
doi:
Substances chimiques
EPHA2 protein, human
0
Ephrin-A2
0
Guanine Nucleotide Exchange Factors
0
Phosphoserine
17885-08-4
Receptor, EphA2
EC 2.7.10.1
CDC2 Protein Kinase
EC 2.7.11.22
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
112207Informations de copyright
Copyright © 2020. Published by Elsevier Inc.