Mechanistic Target of Rapamycin Complex 2

A multiprotein complex consisting of mTOR KINASE; MLST8 PROTEIN; rapamycin-insensitive companion of mTOR protein (RICTOR PROTEIN); and PRR5 (proline-rich protein 5). Like mTORC1, it also regulates cell growth and proliferation in response to growth factors but may not be as sensitive to nutrient availability and is insensitive to SIROLIMUS. In contrast to mTORC1, it can regulate the ACTIN CYTOSKELETON through RHO GTPASES to promote the formation of STRESS FIBERS. The mTORC2 complex also plays a critical role in AKT1 PROTEIN KINASE phosphorylation and activation.

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Networked: 777 relevant articles (33 outcomes, 93 trials/studies)

Relationship Network

Bio-Agent Context: Research Results

Experts

1.	Mischel, Paul S: 15 articles (01/2020 - 11/2011)
2.	Hall, Michael N: 12 articles (11/2021 - 01/2007)
3.	Cavenee, Webster K: 11 articles (01/2020 - 11/2011)
4.	Masui, Kenta: 11 articles (01/2020 - 10/2013)
5.	Wei, Wenyi: 8 articles (01/2022 - 11/2013)
6.	Jacinto, Estela: 8 articles (01/2021 - 07/2011)
7.	Dai, Chunsun: 8 articles (01/2020 - 07/2014)
8.	Su, Bing: 8 articles (01/2020 - 07/2011)
9.	Gera, Joseph: 8 articles (01/2019 - 12/2007)
10.	Jhanwar-Uniyal, Meena: 7 articles (01/2022 - 10/2009)

Related Diseases

1.	Neoplasms (Cancer) 11/12/2021 - "We conclude that MAPK6 can promote cancer by activating AKT independent of mTORC2 and targeting MAPK6, either alone or in combination with mTOR blockade, may be effective in cancers." 01/01/2018 - "Genetic models suggest that selective mTORC2 inhibition would be effective in breast cancers, but the lack of selective small-molecule inhibitors of mTORC2 have precluded testing of this hypothesis to date. " 09/26/2018 - "In contrast, portulaca oleracea oil exhibited protective effects by anti-inflammatory properties via the PI3K/Akt/mTORC2 pathway with a deviation immune response to Th1 to treat atopic diseases and cancer. " 10/01/2023 - "Recent studies have shown the central role of mTOR complex 2 (mTORC2) as a pro-tumourigenic factor of the PI3K/AKT/mTOR pathway in a number of cancers. " 01/01/2019 - "As mTORC2-specific inhibitors do not yet exist, studies into the role of mTORC2 in cancer are performed by deleting Rictor or by RNAi-mediated Rictor silencing. "
2.	Inflammation (Inflammations) 01/01/2019 - "The absence of mTORC2 in dermal γδT cells, but not STAT3, ameliorates skin inflammation. " 09/01/2013 - "In this study, we investigated whether adipose-specific deletion of rictor and thereby inactivation of mTORC2 in PVAT may modulate vascular function by increasing inflammation in PVAT. " 01/01/2021 - "Nevertheless, during inflammation, rictor/mTORC2 signaling declines and Akt activity is reduced. " 01/01/2020 - "Overall, these results demonstrate that mTORC2 signaling protects against renal inflammation and dictates the outcome of AKI by modulating Yap/Taz degradation." 01/01/2020 - "Overexpression of constitutively active Taz (Taz-S89A) could attenuate the inflammation-amplified role of mTORC2 blockage. "
3.	Seizures (Absence Seizure) 01/01/2023 - "We found that mTORC2 inhibition improved or rescued all morphologic effects of Pten loss in the dentate gyrus, but synaptic changes and seizures persisted. " 11/14/2023 - "However, mTOR complex 2 (mTORC2) is also activated in the epileptic brain, and little is known about its role in seizures. " 01/01/2023 - "An established, early postnatal mouse model of PTEN loss in male and female mice showed spontaneous seizures that were not prevented by mTORC2 inactivation. " 01/01/2023 - "Here, we tested the hypothesis that genetic inactivation of the mTORC2 complex via deletion of Rictor is sufficient to rescue morphologic and electrophysiological abnormalities in the dentate gyrus caused by PTEN loss, as well as generalized seizures. " 01/01/2023 - "mTORC2 Inhibition Improves Morphological Effects of PTEN Loss, But Does Not Correct Synaptic Dysfunction or Prevent Seizures."
4.	Type 2 Diabetes Mellitus (MODY) 02/01/2008 - "To examine whether genetic variations in genes encoding components of this signaling pathway contribute to increased susceptibility to type 2 diabetes, we screened STK11 (LKB1) and CRTC2 (TORC2) genes for genetic variants and conducted a case-control study in 1787 unrelated Japanese individuals. " 02/01/2008 - "Single nucleotide polymorphisms in genes encoding LKB1 (STK11), TORC2 (CRTC2) and AMPK alpha2-subunit (PRKAA2) and risk of type 2 diabetes." 10/20/2005 - "Individuals with type 2 diabetes often exhibit fasting hyperglycaemia due to elevated gluconeogenesis; compounds that enhance TORC2 phosphorylation may offer therapeutic benefits in this setting." 03/01/2009 - "These data propose that dysregulation of TORC2 would further exaggerate insulin resistance and promote type 2 diabetes in a LIPIN1-dependent manner." 01/01/2017 - "Inhibition of mTORC1-S6K1 signalling improved GSIS and restored mTORC2 activity in islets from patients with type 2 diabetes as well as in islets isolated from diabetic db/db mice and mice fed a high-fat/high-sucrose diet. "
5.	Breast Neoplasms (Breast Cancer) 01/01/2019 - "In vivo studies conducted on 4T1/BALB/c mouse orthotropic model of breast cancer further corroborated these observations wherein i.v. reintroduction of mTORC2 abrogated monocytes into orthotropic mouse model resulted in diminished acquisition of M2 specific attributes by tumor associated macrophages. " 01/01/2017 - "Furthermore, our study provides a mechanistic link for ER-α-dependent O2.- potentiation and resultant mTORC2 activation in breast cancer cells." 01/01/2023 - "Together, our findings suggest that, whereas the Ras-mediated activation of mTORC2 is expected to play a minor role in breast tumor formation, the Ras-mTORC2 pathway plays an important role in promoting the migration and invasion of breast cancer cells." 01/01/2023 - "Using HER2 and oncogenic Ras-transformed breast epithelial MCF10A cells, we found that both wild-type Ras and oncogenic Ras promote mTORC2 activation and an mTORC2-dependent migration and invasion in these breast cancer models. " 01/01/2023 - "We observed that both Ras and mTORC2 promote the migration of different breast cancer cells and breast cancer cell models. "

Related Drugs and Biologics

1.	Mechanistic Target of Rapamycin Complex 1
2.	Sirolimus (Rapamycin)
3.	Phosphotransferases (Kinase)
4.	MTOR Inhibitors
5.	vistusertib
6.	TOR Serine-Threonine Kinases
7.	Glucose (Dextrose)
8.	CC-223
9.	AICA ribonucleotide (ZMP)
10.	DNA (Deoxyribonucleic Acid)

Related Therapies and Procedures

1.	Drug Therapy (Chemotherapy)
2.	Therapeutics
3.	Cryotherapy (Therapy, Cold)
4.	Chemoprevention
5.	Lasers (Laser)