What is the Difference Between mTORC1 and mTORC2

The key difference between mTORC1 and mTORC2 is that mTORC1 is a rapamycin-sensitive protein complex that regulates protein synthesis in the cell, while mTORC2 is a rapamycin-insensitive protein that regulates cell proliferation and survival, cell migration, and cytoskeletal remodelling.

mTOR is the mechanistic target of rapamycin or mammalian target of rapamycin. It is a kinase enzyme encoded by the mTOR gene in humans. Generally, mTOR links with other proteins and serves as a core component of two distinct protein complexes: mTORC1 and mTORC2. Therefore, being a core component of both complexes, mTOR functions as a serine/threonine protein kinase that regulates the cell’s growth, proliferation, motility survival, protein synthesis, autophagy, and transcription.

CONTENTS

1. Overview and Key Difference
2. What is mTORC1 
3. What is mTORC2
4. Similarities – mTORC1 and mTORC2
5. mTORC1 vs mTORC2 in Tabular Form
6. Summary – mTORC1 vs mTORC2

What is mTORC1?

mTORC1 or mammalian target of rapamycin complex 1 is a rapamycin-sensitive protein complex formed by serine/threonine kinase mTOR. It regulates the protein synthesis in the cell. Structurally, it is a protein complex comprising several components such as mTOR, raptor (regulatory associated protein of mTOR), PRAS40 (proline-rich AKT substrate 40 kDa), and mLST8 (mammalian lethal with sec-13). This protein complex basically functions as a nutrient/energy/redox sensor and controls protein synthesis.

The function of this protein complex is tightly regulated by rapamycin, insulin, growth factors, phosphatidic acid, certain amino acids, and their derivatives such as L-leucine and β-methylbutyric acid, mechanical stimuli, and oxidative stress. Generally, the role of mTORC1 is to activate the translation of proteins. In order to activate mTORC1 for protein production, the cells must have adequate energy resources, nutrient availability, oxygen abundance, and proper growth factors. Furthermore, these resources are extremely critical in order to initiate mRNA translation.

What is mTORC2?

mTORC2 or mTOR complex 2 is a rapamycin-insensitive protein complex formed by serine/threonine kinase mTOR. It regulates cell proliferation and survival, cell migration, and cytoskeletal remodelling. This complex is large and contains seven protein subunits, including catalytic mTOR subunit, DEP domain-containing mTOR interacting protein (DEPTOR), mammalian lethal with SEC13 protein 8 (MLST8, also known as GβL), TTI1/TEL2, rictor, MSINI, and protein observed with rictor 1 and 2 (Protor1/2).

The function of mTORC2 is less understood than mTORC1. However, it has been shown to respond to growth factors in order to modulate cell metabolism and survival. This complex also plays a role as an important regulator in the organization of the actin cytoskeleton through its stimulation of F-actin stress fibers, paxillin, RhoA, Rac1, Cdc42, and protein kinase C α (PKCα). mTORC2 also regulates cellular proliferation and metabolism. Furthermore, mTORC2 activity has been implicated in the regulation of autophagy. In addition, tyrosine activity of mTORC2 phosphorylates IGF-IR and insulin receptors at the tyrosine residues Y1131/1136 and Y1146/1151, which respectively leads to the full activation of IGF-IR and InsR.

What are the Similarities Between mTORC1 and mTORC2?

• mTORC1 and mTORC2 are two protein complexes.
• They are large molecules.
• They play important functions in the cells.
• MLST8 and DEPTOR subunits are shared by both mTORC1 and mTORC2.
• The difference in normal functions of mTORC1 and mTORC2 leads to pathological conditions such as cancer, type 2 diabetes, and neurodegeneration.

What is the Difference Between mTORC1 and mTORC2?

mTORC1 is a rapamycin-sensitive protein complex formed by serine/threonine kinase mTOR that regulates protein synthesis in the cell, while mTORC2 is a rapamycin-insensitive protein complex formed by serine/threonine kinase mTOR that regulates cell proliferation and survival, cell migration and cytoskeletal remodelling. Thus, this is the key difference between mTORC1 and mTORC2. Furthermore, mTORC1 has six subunits, while mTORC2 has seven subunits.

The below infographic presents the differences between mTORC1 and mTORC2 in tabular form for side by side comparison.

Summary – mTORC1 vs mTORC2

mTORC1 and mTORC2 are two protein complexes that have mTOR as the core component. mTORC1 is a rapamycin-sensitive protein complex, and it regulates the protein synthesis in the cell. mTORC2 is a rapamycin-insensitive protein complex, and it regulates cell proliferation and survival, cell migration, and cytoskeletal remodelling. So, this summarizes the difference between mTORC1 and mTORC2.

Reference:

1. “Mammalian Target of Rapamycin Complex 1.” An Overview | ScienceDirect Topics.
2. Oh, Won Jun, and Estela Jacinto. “MTOR Complex 2 Signaling and Functions.” Cell Cycle (Georgetown, Tex.), Landes Bioscience, 15 July 2011.

Image Courtesy:

1. “Activation of mTORC1 at the Lysosome” By Flemingrjf at English Wikipedia (CC BY-SA 3.0) via Commons Wikimedia
2. “RICTOR action” By Kldextraze – Own work (CC BY-SA 3.0) via Commons Wikimedia