**4. PI3K/Akt signaling pathway and its participation in apoptosis inhibition**

As previously mentioned, MAPK p38 and JNK play an important role in apoptosis induction. On the other hand, PI3K activation promotes cellular survival. PI3K is a heterodimer formed by a p85 regulatory subunit and a p110 catalytic subunit responsible for phosphate transfer. The signaling pathway initiated by this kinase is activated by different stimuli, with growth factors standing out among them. Once a ligand binds to the tyrosine specific tyrosine-kinase receptor, an IRS adaptor protein is activated, which in turn activates the regulatory PI3K subunit and generates a conformational change that allows the binding of the catalytic subunit and thus the assembly of the active molecule that catalyzes the conversion of PIP2 into PIP3

[83, 84]. PIP3 interacts with the pleckstrine homology (PH) domain, located in the N-terminal region of the serine/threonine kinase Akt or PKB, with the final result of the kinase being recruited to the plasma membrane [85–87]. Furthermore, PDK1 phosphorylates Akt/PKB producing a conformational change that facilitates a second phosphorylation by the rictormTOR1 complex [88]. Finally, the PI3K/Akt pathway leads to diverse effects associated with cellular proliferation and survival [89, 90]. Specifically, it produces the inactivation of many proapoptotic signals, such as BAD, procaspase-9, and FKHR (Forkhead) transcription factors [21, 91]. It also promotes the activation of CREB, NF-κB, and HIF-1α transcription factors, which in turn activate the expression of antiapoptotic genes [92–94].
