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

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.