New Insights into the Regulation of mTOR Signaling via Ca-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) is important as a second messenger in various biological processes, and its intracellular concentration is tightly regulated. Although the involvement of Ca 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 homeostasis and mTOR activation in pathological hypertrophy has heightened the importance in understanding Ca-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-binding proteins, particularly calmodulin (CaM).