Phosphorylation of CLK2 at serine 34 and threonine 127 by AKT controls cell survival after ionizing radiation.
AKT phosphorylates components of the intrinsic cell survival machinery and promotes survival to various stimuli. In the present study, we identified CDC-like kinase 2 (CLK2) as a new substrate of AKT activation and elucidated its role in cell survival to ionizing radiation. AKT directly binds to and phosphorylates CLK2 on ... serine 34 and threonine 127, in vitro and in vivo. CLK2 phosphorylation was detected in HeLa cells overexpressing active AKT. In addition, we demonstrated that ionizing radiation induces CLK2 phosphorylation via AKT activation. In contrast, the suppression of endogenous AKT expression by siRNA inhibited CLK2 phosphorylation in response to 2 gray of γ-ray or insulin. Furthermore, we examined the effect of CLK2 on the survival of irradiated CCD-18Lu cells overexpressing Myc-CLK2. CLK2 overexpression significantly increased cell growth and inhibited cell death induced by 2 gray. The role of CLK2 in cell survival to ionizing radiation was dependent on the phosphorylation of serine 34 and threonine 127. Our results suggest that AKT activation controls cell survival to ionizing radiation by phosphorylating CLK2, revealing an important regulatory mechanism required for promoting cell survival.
Mesh Terms:
Cell Death, Cell Survival, Enzyme Activation, Gamma Rays, Gene Silencing, HeLa Cells, Humans, Hypoglycemic Agents, Insulin, Phosphorylation, Protein-Serine-Threonine Kinases, Protein-Tyrosine Kinases, Proto-Oncogene Proteins c-akt, RNA, Small Interfering
Cell Death, Cell Survival, Enzyme Activation, Gamma Rays, Gene Silencing, HeLa Cells, Humans, Hypoglycemic Agents, Insulin, Phosphorylation, Protein-Serine-Threonine Kinases, Protein-Tyrosine Kinases, Proto-Oncogene Proteins c-akt, RNA, Small Interfering
J. Biol. Chem.
Date: Oct. 08, 2010
PubMed ID: 20682768
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