Defective regulation of Ca2+/calmodulin‐dependent protein kinase II in γ‐irradiated ataxia telangiectasia fibroblasts

FEBS Letters

Paterson, Malcolm C¹  Famulski, Konrad S¹ 

[1] Department of Biological and Medical Research (MBC 03), King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh 11211, Saudi Arabia

关键词: Ataxia telangiectasia;    Calmodulin-dependent protein kinase II;    DNA synthesis;    Intracellular Ca2+ mobilization;   

DOI  :  10.1016/S0014-5793(99)00664-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Recent indirect evidence suggests that a Ca²⁺/calmodulin-dependent pathway, which may involve calmodulin-dependent protein kinase II (CaMKII), mediates the S-phase delay manifested by γ-ray-exposed human fibroblasts. This pathway is severely impaired in ataxia telangiectasia (A-T) cells [Mirzayans et al. (1995) Oncogene 11, 1597]. To extend these findings, we assayed CaMKII activity in irradiated normal and A-T fibroblasts. The radiation treatment induced the autonomous activity of the kinase in normal cells. In contrast, this activity was not elevated in either (i) normal cells pretreated with the selective CaMKII antagonist KN-62 or (ii) γ-irradiated A-T cells. Moreover, A-T fibroblasts, unlike normal cells, failed to mobilize intracellular Ca²⁺ upon mitogenic stimulation. These findings identify a novel role for CaMKII in radiation-induced signal transduction and suggest its involvement in effecting the S-phase delay. The data also implicate ATM, the product of the gene responsible for A-T, as a key mediator of both intracellular Ca²⁺ mobilization and CaMKII activation in response not only to genotoxic stress but also to physiological stimuli.

【 授权许可】

Unknown