11T1 Growth factor Growth factor receptor РІЗК PIP2 PIP.. PTEN Enzymatic conversion Activation Inactivtion ►Leads to activation AKT PRAS40 mTOR Other targets PKCα
Mechanistic target of rapamycin (mTOR) is a protein kinase that is a central regulator of cell division and cellular
In healthy cells, signaling downstream of growth factor receptors leads to the activation of PI3 kinase (PI3K), which phosphorylates lipid targets such as PIP2, forming PIP3. These lipids recruit a kinase called AKT to the cell membrane, where it is phosphorylated and activated. In turn, AKT phosphorylates and inactivates PRAS40. PRAS40 is normally bound to mTOR, inhibiting its activity. Thus, inactivation of PRAS40 activates mTOR. A schematic of this signaling pathway is shown below.
Which of the following mutations is most likely to increase activation of mTOR?
- a mutation that decreases the activity of PTEN, a phosphatase that dephosphorylates the lipid PIP3
- a mutation that increases expression of PKCα, which is phosphorylated by mTOR
- a mutation in a growth factor receptor that decreases its ability to bind its ligand
- a mutation in mTOR that decreases its ability to bind to its substrates
- a mutation in AKT that prevents it from being phosphorylated
- a mutation in PRAS40 that increases its affinity for mTOR
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