Rictor
Defining subunit of mTORC2 (Rapamycin-Insensitive Companion of mTOR); routes mTOR toward Akt and the cytoskeleton rather than S6K1/4E-BP1.
The part that makes mTOR into mTORC2. The defining building block of mTORC2 (the second mTOR complex) - without it, you don't have mTORC2. It steers mTOR signaling toward Akt and the cell's internal skeleton rather than toward growth/protein-building.
Confers acute rapamycin insensitivity and, with SIN1, the substrate specificity for Akt S473.
TL;DR. Rictor appears in 12 curated studies in Oliver's mTOR Atlas: 5 in animal models; 6 at the molecular level (cells, biochemistry, structure); 1 review. No study in people is recorded for it in the Atlas yet. It has 1 interaction in the curated pathway model.
In the pathway model
| Interaction | Mechanism | Evidence | Studies |
|---|---|---|---|
| Rictor required-for mTORC2 mechanism: complex-assembly · this link in full · on the map table | Rictor is what makes the second complex, mTORC2, distinct – and rapamycin doesn't block it right away. Holds under: Mammalian cells, Drosophila and conditional Rictor-knockout mice (SAR2004, JAC2004, HUA2013). Shows that the complex needs Rictor; relevance in human tissue is not tested by these studies. plausible in people, not shown directly · settled in the literature | A | SAR2004, JAC2004, HUA2013, POL2015 |
Evidence at a glance
| Evidence | What it means | Studies |
|---|---|---|
| A | Animal model | 5 |
| M | Molecular — cells, biochemistry, structure | 6 |
| R | Review — secondary literature, not a new result | 1 |
No direct human evidence in the Atlas for this entity yet — everything below rests on animal or molecular work.
Studies
| Year | Evidence | Study |
|---|---|---|
| 2015 | A | mTORC1 and mTORC2 selectively regulate CD8+ T cell differentiation POL2015 By deleting Tsc2, Rheb or Rictor in T cells, this work split the CD8 response between the two mTOR complexes. Tsc2 loss left mTORC1 constitutively active: the cells were strongly glycolytic (high ECAR, high Slc2a1 and Pfk1, low spare respiratory capacity), made more IFN-gamma, TNF and granzyme B, cleared EL4 thymoma and slowed B16-OVA growth, but stayed terminally differentiated and were about two-fold fewer than wild type at day 30, with no memory. Rheb loss removed mTORC1 activity with mTORC2 intact: those cells failed as effectors but kept memory-like features and were about two-fold more numerous at day 30, yet did not respond to rechallenge, which the authors trace to metabolic defects. Rapamycin from day 5 (100 ug/kg daily) rescued survival of Tsc2-deficient cells, raised CD127 and Eomesodermin, lowered KLRG1 and T-bet and restored a recall response. Losing mTORC2 by Rictor deletion left effector function intact but increased memory cells that still responded 133 days after infection, and the Tsc2/Rictor double knockout showed that the hyperactive effector phenotype needs mTORC2. Boundary: mouse genetics with TCR-transgenic transfers and transplantable tumours; the comparison rests on genetic extremes (no TSC2, no Rheb, no Rictor) rather than graded physiological signalling, and nothing here is measured in people. |
| 2013 | A | mTORC2 controls actin polymerization required for consolidation of long-term memory HUA2013 Conditional deletion of Rictor in the postnatal mouse forebrain reduced mTORC2 activity and selectively impaired long-term memory and the late phase of hippocampal LTP, with a comparable long-term-memory deficit in dTORC2-deficient flies. Hippocampal actin polymerisation was reduced, and restoring it rescued both L-LTP and long-term memory; a compound that raised mTORC2 activity converted early LTP into late LTP and enhanced memory. This is the loss-of-function AND rescue evidence that mTORC2 is required for memory consolidation - the arm chronic rapamycin also disrupts, and the study Open Question H8 needs for its mTORC2 liability leg, which until 2026-09-05 rested on no supporting study at all. |
| 2012 | A | Hepatic mTORC2 activates glycolysis and lipogenesis through Akt, glucokinase, and SREBP1c HAG2012 The authors deleted rictor, an essential mTORC2 component, only in mouse liver. In fed knockout mice the liver lost Akt Ser473 phosphorylation and had lower glucokinase and SREBP1c activity, so it kept making glucose (gluconeogenesis) while glycolysis and fat synthesis fell, as if it could not sense that the animal had eaten. The mice became hyperglycaemic and hyperinsulinaemic with low blood lipids. In mTORC2-deficient hepatocytes, constitutively active Akt2 restored both glucose flux and lipogenesis, while extra glucokinase restored glucose flux but not lipogenesis, placing Akt as the main route from hepatic mTORC2 to these outputs. Boundary: Mouse liver with lifelong genetic loss of mTORC2, plus cultured mouse hepatocytes. Not a drug study and not tested in people. Drafted from the abstract only. |
| 2011 | A | The kinase mTOR regulates the differentiation of helper T cells through the selective activation of signaling by mTORC1 and mTORC2 DEL2011 mTORC1 and mTORC2 selectively program distinct CD4 helper T-cell lineages. |
| 2008 | A | Skeletal muscle-specific ablation of raptor, but not of rictor, causes metabolic changes and results in muscle dystrophy BEN2008 In mice, muscle-specific raptor loss (not rictor) causes dystrophy, showing mTORC1 is essential for muscle homeostasis. |
| 2026 | M | PTEN regulates microtubule polymerization via mTORC2, but not mTORC1, in peripheral sensory neurons EVA2026 Uses Raptor (mTORC1) versus Rictor (mTORC2) co-deletion on a Pten-knockout background to ask which complex carries the growth signal to the microtubule cytoskeleton. Suppressing mTORC2 — but not mTORC1 — returns the accelerated microtubule polymerisation and neuronal hypertrophy of Pten-KO neurons to wild-type levels, and the effect is confined to the axonal growth cone rather than the proximal axon shaft. A clean genetic dissection on the comparatively thin mTORC2 side of the pathway. |
| 2026 | M | Pdcd4-Rictor interaction suppresses mTORC2-PFKFB3 axis and tumorigenesis in NSCLC. WANG2026B Pdcd4 binds Rictor via residues R105/K108/R110 to disrupt mTORC2 assembly and kinase activity, lowering PFKFB3 levels and suppressing glycolysis and NSCLC tumour growth. |
| 2026 | R | The role of mTORC2/RICTOR in immune cells and inflammatory diseases. XU2026B mTORC2/RICTOR signaling (via AKT, SGK1, PKC) shapes Th1/Th2 differentiation, Treg stability, memory T cell formation, BCR signaling and plasma cell survival, and macrophage/DC/NK function; its role in tissue inflammation is context-dependent (exacerbating osteoarthritis and pancreatitis but restraining pro-inflammatory polarization in colorectal cancer), and dual mTORC1/2 inhibitors (e.g. AZD2014) show early but complicated promise. |
| 2008 | M | The mammalian target of rapamycin complex 2 controls folding and stability of Akt and protein kinase C FAC2008 Cells lacking the mTORC2 components mTOR, SIN1 or rictor lost phosphorylation of Akt and of conventional protein kinase C at the turn motif, a site near the end of the kinase domain. This phosphorylation did not depend on growth factors, and the authors reported the same function in yeast. Turn-motif phosphorylation helped newly made Akt and PKC fold correctly and stay stable; without it, Akt was held by the chaperone Hsp90 and protected from ubiquitin-mediated breakdown. mTORC2 controlled the Akt turn-motif and hydrophobic-motif (Ser473) sites independently in vivo and phosphorylated both directly in vitro. Boundary: Cell culture, yeast and in vitro kinase assays, with mouse tissue for the in vivo site analysis. Shows a protein-maturation role of mTORC2, not an organismal phenotype. Drafted from the abstract only. |
| 2006 | M | Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB SAR2006 The molecular explanation for rapamycin's dark side. Short-term rapamycin only hits mTORC1, but prolonged treatment can also inhibit the assembly of NEW mTORC2 in susceptible cell types, reducing mTORC2 abundance and cutting Akt signaling over time. The wording matters: this is prevention of new assembly, not the dismantling of complexes already built, and the response depends on cell context and length of exposure. This is the mechanistic root of the insulin-resistance side effect later shown in mice (see Lamming 2012) - crucial for anyone dosing rapamycin for longevity. |
| 2006 | M | Ablation in mice of the mTORC components raptor, rictor, or mLST8 reveals that mTORC2 is required for signaling to Akt-FOXO and PKCalpha, but not S6K1 GUE2006 The foundational genetic 'dissection' of the two complexes in living mice. Deleting Raptor was lethal early (mTORC1 essential); deleting Rictor or mLST8 selectively knocked out mTORC2 signaling to Akt and PKCalpha but spared S6K1. This cleanly assigned jobs to each complex and showed mLST8 is an mTORC2-specific requirement in mice. |
| 2004 | M | Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton SAR2004 Discovery of Rictor and the SECOND mTOR complex, mTORC2. Crucially showed this complex is NOT blocked by rapamycin and does not use Raptor - it controls the cytoskeleton via PKC. This is the paper that split mTOR biology into 'two faces' at the molecular level. |
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