Cell Survival Pathway

The RTK-PI3 kinase-Akt pathway can be mutated in a few ways so that it is always "on", even in the absence of an external signal. This pathway inhibits apoptosis. One mutation is a loss of function in Bad, which usually binds the inhibitory protein Bcl2. If Bad cannot bind to Bcl2, Bcl2 can always inhibit apoptosis. Another mutation is a gain of function in Akt. If Akt was always active, it would not need the upstream parts of the pathway to be turned on, and it was always phosphorylate Bad, letting Bcl2 inhibit cell death. The third utation that would lead to this pathway always being on is a lss of function in PTEN, the phosphatase that removes a phosphate group from PIP3. If PIP3 never lost a phosphate, it would always be active, and could dock Akt and PDK1 to the membrane, inititating the rest of the pathway.