What is the Difference Between mTORC1 and mTORC2

The main difference between mTORC1 and mTORC2 is that mTORC1 is sensitive to rapamycin, whereas mTORC2 is sensitive to growth factors.

mTORC1 and mTORC2 are two types of multiprotein complexes of mTOR (mammalian target of rapamycin). Generally, mTOR is a serine-threonine kinase that functions through the two multiprotein complexes; mTORC1 and mTORC2.

Key Areas Covered

1. What is mTORC1
     – Definition, Structure, Function
2. What are mTORC2
     – Definition, Structure, Function
3. Similarities Between mTORC1 and mTORC2
     – Outline of Common Features
4. Difference Between mTORC1 and mTORC2
     – Comparison of Key Differences

Key Terms                                                                                                                  

mTOR, Mammalian Target of Rapamycin, mTORC1, mTORC2

What is mTORC1

mTORC1 is one of the two multiprotein complexes of mTOR that is a serine-threonine kinase. mTOR functions through multiprotein complexes. PI3-K/Akt tightly regulates the function of mTORC1. In addition to that, mTORC1 is sensitive to rapamycin. Generally, rapamycin prevents the formation of cancer in humans and mice. It is called sirolimus. The main function of mTORC1 is to regulate protein synthesis. It also regulates cell growth through downstream molecules. These molecules may include 4E-BP1 and S6K.

Figure 1: mTORC1 Pathway

Furthermore, rapamycin, insulin, phosphatidic acid, some amino acids, and growth factors can regulate the activity of mTORC1. In addition, mechanical stimuli and oxidative stress can also regulate the activity of mTORC1. However, the main function of mTORC1 is the activation of the translation of proteins. Generally, manufacturing proteins is important for the growth and proliferation of cells. In order to produce proteins, cells must have energy sources, oxygen abundance, proper growth factors, and nutrients.    

What is mTORC2

mTORC2 is the other multiprotein complex of mTOR. Although mTORC2 is not sensitive to rapamycin or nutrients,  it is sensitive to growth factors. The main function of mTORC2 is to modulate growth factor signaling. Generally, it is done by phosphorylating the C-terminal hydrophobic motif of some AGC kinases such as Akt and SGK. mTOR2 is also important for the maintenance of normal cells as well as cancer cells. Moreover, it associates with the ribosomes of cells and regulates the metabolism of cells.

Figure 2: mTORC1

In addition to cell proliferation, mTORC2 regulates survival, cytoskeletal remodeling, and cell migration. Normally, the mTORC2 complex is large, containing seven protein subunits.  mTORC1 and mTORC2 share four subunits: catalytic mTOR subunit, mammalian lethal with sec-13 protein 8 (mLST8, also known as GβL), DEP domain-containing mTOR-interacting protein (DEPTOR), and TTI1/TEL2. Rapamycin-insensitive companion of mTOR (RICTOR), protein observed with rictor 1 and 2 (Protor1/2), and mammalian stress-activated protein kinase interacting protein 1 (mSIN1) are the three subunits that are unique to mTORC2.

Similarities Between mTORC1 and mTORC2

• mTORC1 and mTORC2 are two types of multiprotein complexes of mammalian targets of rapamycin (mTOR).
• mTOR is a serine-threonine kinase that functions via two multiprotein complexes: mTORC1 and mTORC2.

Difference Between mTORC1 and mTORC2

Definition

mTORC1 refers to a serine/threonine kinase that is upregulated in certain tumor cell types, while mTORC2 refers to an acutely rapamycin-insensitive protein complex formed by serine/threonine kinase mTOR.

Sensitivity

mTORC1 is sensitive to rapamycin, while mTORC2 is sensitive to growth factors.

Regulation

PI3-K/Akt tightly regulates mTORC1, while mTORC2 is not regulated.

Function

mTORC1 regulates protein synthesis and cell growth through downstream molecules, including 4E-BP1 and S6K, while mTORC2 modulates growth factors, signaling by phosphorylation of the C-terminal hydrophobic motif.

Conclusion                                                      

In brief, mTORC1 and mTORC2 are two types of multiprotein complexes of mTOR that is mammalian target of rapamycin. Generally, mTOR is a serine-kinase, working via the two multiprotein complexes. mTORC1 is sensitive to rapamycin. PI3-K/Akt tightly regulates mTORC1. However, the main function of mTORC1 is to regulate protein synthesis and cell growth through the downstream molecules, including 4E-BP1 and S6K. In comparison, mTORC2 is another multiprotein complex that is sensitive to growth factors. But it is not regulated. In addition, the main function of mTORC2 is to modulate growth factors, signaling by phosphorylation of the C-terminal hydrophobic motif. Therefore, the main difference between mTORC1 and mTORC2 is sensitivity, regulation, and function.                

References:                

1. Jhanwar-Uniyal M, Gillick JL, Neil J, Tobias M, Thwing ZE, Murali R. Distinct signaling mechanisms of mTORC1 and mTORC2 in glioblastoma multiforme: a tale of two complexes. Adv Biol Regul. 2015 Jan;57:64-74. doi: 10.1016/j.jbior.2014.09.004. Epub 2014 Sep 18. PMID: 25442674.

Image Courtesy:

1. “General mTORC1 Pathway” By Flemingrjf at English Wikipedia – Own work (CC BY-SA 3.0) via Commons Wikimedia
2. “5h64” By User:Astrojan – Own Work (CC BY-SA 4.0) via Commons Wikimedia