Mechanism of Akt Signaling

The Akt signaling pathway, also known as the PI3K-Akt pathway, is a signaling cascade that regulates various cellular processes such as cell growth, survival, and metabolism. Here are the main steps in the mechanism of Akt signaling:

• The pathway is activated by growth factors, such as insulin or insulin-like growth factor 1 (IGF-1), binding to their respective receptors on the cell surface.
• This binding leads to the activation of a class of enzymes called phosphoinositide 3-kinases (PI3Ks), which phosphorylate a lipid called phosphatidylinositol 4,5-bisphosphate (PIP2) to form phosphatidylinositol 3,4,5-trisphosphate (PIP3).
• PIP3 then recruits Akt, also known as protein kinase B (PKB), to the cell membrane via its binding to pleckstrin homology (PH) domains on the Akt protein.
• Once recruited to the membrane, Akt is activated by phosphorylation at a specific site by a protein called PDK1.
• Activated Akt can then phosphorylate and regulate a variety of downstream targets, including mTOR, GSK3, and various transcription factors to promote cell growth, survival, and metabolism.
• Akt also can inactivate the FOXO family of transcription factors by phosphorylating them, leading to inhibition of pro-apoptotic genes and cell-cycle arrest, hence promoting cell survival.
• Akt also can phosphorylate mTOR (mammalian target of rapamycin), leading to activation of the mTORC1 complex which in turn leads to protein synthesis, cell growth, and proliferation.
• In a negative feedback loop, Akt can inhibit the activity of PI3K via phosphorylation and inactivation of the regulatory subunit p85. This helps to fine-tune the duration and strength of the Akt signaling response.
• The Akt signaling pathway is tightly regulated by multiple mechanisms such as phosphatase activity, ubiquitination, and protein degradation.

It is important to notice that the Akt pathway has many crosstalks with other pathways, that may be activated or inhibited by it. The Akt pathway is also a target of many cancer therapies, as its activation is linked to cancer progression.

Akt, also known as protein kinase B, is a signaling protein that plays a key role in many cellular processes, including cell growth, proliferation, and survival. It is activated by a variety of stimuli, including growth factors, hormones, and stress signals, and it functions by phosphorylating (adding a phosphate group to) a variety of downstream proteins, which leads to changes in their activity.