mTOR pathway

The mTOR pathway follows the principles of the PI-3 kinase pathway.

mTOR pathway- Introduction:

For a multicellular organism to grow, its cells must grow. If the cells simply divided without growing, they would get progressively smaller. Extracellular signals are generally required for the animal cells to grow and divide, as well as to survive. The PI-3 kinase -Akt pathway that signals cells to grow depends on a large, serine/threonine protein kinase called TOR (named as the Target of Rapamycin).

In mammalian cells, it is called mTOR. TOR exists in two functionally distinct multiprotein complexes. In mammalian cells, mTOR complex 1 (mTORC1) contains the protein raptor; this complex is sensitive to rapamycin and induces cell growth by augmenting protein synthesis and preventing protein degradation.

mTOR pathway- mechanism of action:

1. mTOR augments protein synthesis by phosphorylating the eIF4E-binding protein 1 (4E-BP1).
2. The phosphorylation of 4E-BP1 inhibits its binding to eIF4E, enabling eIF4E to trigger cap-dependent translation.
3. mTOR complex 2 contains the protein rictor and is insensitive to rapamycin.
4. Then it helps to activate Akt and it controls the actin cytoskeleton via Rho family GTPases.
5. In the presence of the extracellular growth factors, activation of mTORC1 happens via the PI-3 kinase -Akt pathway.
6. Akt activates mTOR in complex 1 indirectly by phosphorylating, and thereby preventing, a GAP called TSC2. TSC2 acts on a monomeric RAS -related GTPase Rheb.
7. Rheb in its active form (Rheb-GTP) activates mTOR. The net result is that Akt activates mTOR and thereby triggers the cell growth.

The schematic representation of the activation of mTOR by the PI-3 kinase-Akt signaling pathway:

Other related notes:

1. RAS-MAP kinase pathway: https://thebiologyislove.com/ras-map-kinase-pathway/
2. PI-3 kinase pathway: https://thebiologyislove.com/pi-3-kinase-pathway/
3. Insulin Signaling pathway: https://thebiologyislove.com/insulin-signaling-pathway-pi-3-kinase-pathway/

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