c‐Abl kinase regulates cell proliferation and ionizing radiation‐induced G2/M arrest via phosphorylation of FHL2

FEBS Open Bio

Xiayang Niu¹  Di Wang¹  Guang‐Fei Wang²  Xuan Liu²  Hainan Liu²  Qincai Dong²  Yebao Yao²  Cheng Cao² 

[1] Anhui University, Hefei, China;Beijing Institute of Biotechnology, China;

关键词: c‐Abl;    cell proliferation;    FHL2;    G2/M arrest;    phosphorylation;   

DOI  :  10.1002/2211-5463.13177

来源: Wiley

【 摘 要 】

Nonreceptor tyrosine kinase c‐Abl participates in several cellular processes by phosphorylating transcription factors or cofactors. c‐Abl binds and phosphorylates four‐and‐a‐half‐LIM‐only protein 2 (FHL2), but the identity of the phosphorylation sites and their contribution to cell cycle regulation is unclear. In this study, we demonstrate that c‐Abl highly phosphorylates FHL2 at Y97, Y176, Y217, and Y236 through mass spectrometry and tyrosine‐to‐phenylalanine (Y → F) mutant analysis. Proliferation was inhibited in cells expressing wild‐type (WT) FHL2 but not cells expressing the phosphorylation‐defective mutant FHL2(4YF). Moreover, FHL2 contributed to cell cycle arrest at G2/M induced by ionizing radiation (IR). FHL2 WT but not FHL2(4YF) rescued FHL2 function in FHL2‐depleted cells by causing IR‐induced G2/M arrest. These results demonstrate that c‐Abl regulates cell cycle progression by phosphorylating FHL2.

【 授权许可】

CC BY