New Insights into the Regulation of mTOR Signaling via Ca(2+)-Binding Proteins

Environmental factors are important regulators of cell growth and proliferation. Mechanistic target of rapamycin (mTOR) is a central kinase that maintains cellular homeostasis in response to a variety of extracellular and intracellular inputs. Dysregulation of mTOR signaling is associated with many diseases, including diabetes and cancer. Calcium ion (Ca(2+)) is important as a second messenger in various biological processes, and its intracellular concentration is tightly regulated. Although the involvement of Ca(2+) mobilization in mTOR signaling has been reported, the detailed molecular mechanisms by which mTOR signaling is regulated are not fully understood. The link between Ca(2+) homeostasis and mTOR activation in pathological hypertrophy has heightened the importance in understanding Ca(2+)-regulated mTOR signaling as a key mechanism of mTOR regulation. In this review, we introduce recent findings on the molecular mechanisms of regulation of mTOR signaling by Ca(2+)-binding proteins, particularly calmodulin (CaM).