RICTORmTORC2

RICTOR-mTORC2, commonly referred to as mTORC2, is a multiprotein kinase complex in which RICTOR defines the complex’s identity. It is one of two major mTOR-containing complexes in mammals, the other being mTORC1, which contains RAPTOR. The core components of mTORC2 typically include mTOR, RICTOR, mLST8 (GβL), and MAPKAP1 (SIN1); regulatory variants may include PROTOR1/2 (PRR5/PRR5L) in some cells.

Functions of mTORC2 center on phosphorylation of AGC family kinases, notably AKT at Ser473, as well as SGK1 and PKCα. Through these substrates, mTORC2 influences cell survival, metabolism, and cytoskeletal organization, affecting processes such as actin dynamics, cell migration, and potentially mitochondrial function. The complex thereby connects growth factor signaling to downstream kinase networks.

Regulation and localization: mTORC2 is generally activated by growth factors and PI3K signaling. It is considered rapamycin-insensitive in the short term, although prolonged rapamycin exposure can disrupt assembly of mTORC2 in some contexts. The complex is found in the cytoplasm and at membranes associated with the cytoskeleton, where it can respond to signals that regulate cell shape and movement.

Biological significance: mTORC2 signaling contributes to normal development and homeostasis, and dysregulation has been linked to cancer, metabolic diseases, and aging. Because of its distinct substrate profile and regulatory mechanisms, mTORC2 represents a separate node in mTOR signaling with potential therapeutic relevance in diseases driven by AKT- or SGK1-related pathways.

History: The name RICTOR reflects its original designation as the rapamycin-insensitive companion of mTOR, identifying it as a defining component of the mTORC2 complex in the early 2000s.