RRC ID 61360
Author Kaibori Y, Katayama K, Tanaka Y, Ikeuchi M, Ogawa M, Ikeda Y, Yuki R, Saito Y, Nakayama Y.
Title Kinase activity-independent role of EphA2 in the regulation of M-phase progression.
Journal Exp Cell Res
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.
Volume 395(2)
Pages 112207
Published 2020-10-15
DOI 10.1016/j.yexcr.2020.112207
PII S0014-4827(20)30456-0
PMID 32750331
MeSH 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
IF 3.383
DNA material pCMV-VSV-G-RSV-Rev (RDB04393) pCAG-HIVgp (RDB04394)