New Insights into the Regulation of mTOR Signaling via Ca2+-Binding Proteins

Int J Mol Sci. 2023 Feb 15;24(4):3923. doi: 10.3390/ijms24043923.

Abstract

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 (Ca2+) is important as a second messenger in various biological processes, and its intracellular concentration is tightly regulated. Although the involvement of Ca2+ mobilization in mTOR signaling has been reported, the detailed molecular mechanisms by which mTOR signaling is regulated are not fully understood. The link between Ca2+ homeostasis and mTOR activation in pathological hypertrophy has heightened the importance in understanding Ca2+-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 Ca2+-binding proteins, particularly calmodulin (CaM).

Keywords: Ca2+ mobilization; TSC2; calmodulin; mTOR.

Publication types

  • Review

MeSH terms

  • Calcium / metabolism
  • Calmodulin / metabolism
  • Carrier Proteins / metabolism
  • Signal Transduction
  • Sirolimus
  • TOR Serine-Threonine Kinases* / metabolism

Substances

  • Calcium
  • Calmodulin
  • Carrier Proteins
  • Sirolimus
  • TOR Serine-Threonine Kinases