TORC2 signaling

Definition

Target type: biologicalprocess

A series of intracellular molecular signals mediated by TORC2; TOR (rapamycin-insensitive companion of TOR) in complex with at least Rictor (regulatory-associated protein of TOR), or orthologs of, and other signaling components. [GOC:lb]

TORC2 signaling is a critical cellular pathway that regulates diverse cellular processes, including cell growth, survival, and metabolism. It is activated by growth factors and nutrients, leading to the phosphorylation of downstream substrates that influence these processes. Here\\'s a detailed breakdown of TORC2 signaling:

**1. TORC2 Composition:**
- TORC2 is a multiprotein complex comprised of:
- **TOR (Target of Rapamycin):** A serine/threonine protein kinase that acts as the catalytic core of the complex.
- **RICTOR (Rapamycin-insensitive companion of mTOR):** A scaffolding protein essential for TORC2 assembly and function.
- **mLST8 (Mammalian lethal with SEC13 protein 8):** Acts as a regulatory subunit, contributing to the stability and activity of the complex.
- **Sin1 (Stress-activated protein kinase interacting protein 1):** Plays a crucial role in TORC2 activation and substrate specificity.
- **Protor-1/2 (Protein observed with TOR-1/2):** Act as scaffolding proteins involved in TORC2 assembly and recruitment to specific cellular locations.

**2. Activation Mechanisms:**
- **Growth factor stimulation:** Growth factors like insulin and IGF-1 activate the PI3K/AKT pathway, which in turn phosphorylates and activates mTORC2.
- **Nutrient availability:** High levels of nutrients, such as glucose and amino acids, also contribute to TORC2 activation by influencing the PI3K/AKT pathway and other downstream signaling events.

**3. Downstream Targets and Effects:**
- **AKT phosphorylation:** TORC2 directly phosphorylates AKT at Ser473, a crucial step in AKT activation. Activated AKT promotes cell survival, growth, and metabolism by modulating various downstream targets.
- **Rho GTPases:** TORC2 activates Rho GTPases, including RhoA, Rac1, and Cdc42, which regulate cytoskeletal organization and cell migration.
- **PKCα:** TORC2 activates PKCα, a protein kinase involved in cell survival, growth, and metabolism.
- **SGK1:** TORC2 activates SGK1 (serum/glucocorticoid-regulated kinase 1), a kinase involved in ion transport and cell survival.
- **Other targets:** TORC2 has been implicated in regulating various other cellular processes, including autophagy, mitochondrial function, and immune responses.

**4. Regulation and Feedback Loops:**
- **Negative feedback:** TORC2 signaling can be negatively regulated by its own downstream effectors, such as AKT and SGK1, creating feedback loops that maintain cellular homeostasis.
- **TSC2:** The TSC1/TSC2 complex, a negative regulator of TORC1, can also indirectly regulate TORC2 activity by modulating the availability of Rheb, a positive regulator of mTOR.
- **AMPK:** AMP-activated protein kinase (AMPK) acts as a sensor of cellular energy status and can inhibit TORC2 signaling in response to energy stress.

**5. Physiological Roles and Implications:**
- **Cell growth and proliferation:** TORC2 signaling is crucial for cell growth, proliferation, and survival by regulating AKT and other downstream targets.
- **Metabolism:** TORC2 plays a role in regulating glucose metabolism, lipid synthesis, and protein synthesis.
- **Organ development and function:** TORC2 signaling is important for normal organ development and function, including the heart, brain, and immune system.
- **Disease implications:** Dysregulation of TORC2 signaling has been implicated in various diseases, including cancer, diabetes, and neurodegenerative disorders.'
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Proteins (2)

Compounds (10)