Protein Kinases and Phosphatases in the Control of Cell Fate

Figure 1

PI3K signalling pathway: The phosphatidylinositol 3-kinase (PI3K) signalling pathway begins with PI3K activation by receptor tyrosine kinases after growth factors or insulin stimulation. PI3K activity phosphorylates and converts the lipid second messenger phosphatidylinositol 4,5-bisphosphate (PIP2—indicated by red phosphoinositide) into phosphatidylinositol 3,4,5-triphosphate (PIP3—indicated by green phosphoinositide), with consequent double phosphorylation/activation of Akt kinase. Akt promotes cell proliferation and survival by phosphorylation/inhibition of several proapoptotic targets (hold by the red dotted line), or by activation of mTOR complex 1, an important regulator of several processes, such as autophagy, angiogenesis and protein synthesis. Protein phosphatase 2a (PP2a) family members are able to dephosphorylate/inhibit Akt, favouring apoptosis also by direct dephosphorylation of Bcl-2. The tumour suppressor phosphatase PTEN negatively regulates PI3K signalling by dephosphorylating PIP3, converting it back to PIP2. A mono-uniquitinated/active form of PTEN is able to translocate into the nucleus, promoting DNA repair, cell cycle arrest and chromosome stability.