Akt

Definition

Akt, also known as protein kinase B (PKB), is a crucial serine/threonine kinase that plays a significant role in various cellular processes, including metabolism, growth, survival, and angiogenesis. It is primarily activated through signaling pathways initiated by receptor tyrosine kinases (RTKs) and G protein-coupled receptors (GPCRs), leading to its phosphorylation and subsequent activation. This activation enables Akt to phosphorylate a wide range of substrates, influencing critical biological functions and contributing to the regulation of cell cycle progression and apoptosis.

5 Must Know Facts For Your Next Test

1. Akt is activated by the binding of PIP3 to its pleckstrin homology (PH) domain, leading to its translocation to the plasma membrane.
2. Once activated, Akt phosphorylates key substrates involved in glucose metabolism, cell proliferation, and survival signaling.
3. Akt signaling is often upregulated in various cancers, making it a potential target for therapeutic interventions.
4. Akt can inhibit apoptosis by phosphorylating and inactivating pro-apoptotic factors such as Bad and caspase-9.
5. The balance of Akt activity is crucial for cellular homeostasis; excessive activation can lead to uncontrolled cell growth and cancer.

Review Questions

• How does Akt interact with receptor tyrosine kinases in the signaling pathway?
  • Akt interacts with receptor tyrosine kinases through the PI3K pathway. When a ligand binds to an RTK, it activates PI3K, which produces PIP3. This lipid molecule recruits Akt to the plasma membrane, where it undergoes phosphorylation by 3-phosphoinositide-dependent protein kinase-1 (PDK1) and mTOR. This process amplifies the signaling cascade initiated by the RTK, ultimately leading to various cellular responses such as growth and survival.
• Discuss the implications of aberrant Akt signaling in cancer development.
  • Aberrant Akt signaling plays a critical role in cancer development due to its ability to promote cell survival and growth. Many cancers exhibit hyperactivation of Akt, which can result from mutations in upstream regulators like PTEN or increased expression of RTKs. This enhanced Akt activity leads to inhibition of apoptosis and uncontrolled proliferation, contributing to tumorigenesis. Targeting the Akt pathway has emerged as a promising strategy in cancer therapy aimed at restoring normal cell death processes and inhibiting tumor growth.
• Evaluate the role of Akt in maintaining cellular homeostasis and how dysregulation may lead to pathological conditions.
  • Akt plays a vital role in maintaining cellular homeostasis by regulating processes such as metabolism, growth, and apoptosis. Its ability to promote survival signals ensures that cells respond appropriately to growth factors while preventing unnecessary cell death. However, dysregulation of Akt signaling—such as overactivation—can disrupt this balance, leading to pathological conditions like cancer or metabolic disorders. Understanding these mechanisms highlights the importance of targeted therapies that can modulate Akt activity to restore normal cellular function.

Related terms

Phosphatidylinositol 3-kinase (PI3K): An important enzyme that is activated by receptor tyrosine kinases, PI3K generates phosphatidylinositol (3,4,5)-trisphosphate (PIP3), which recruits Akt to the plasma membrane for activation.

mTOR: Mammalian target of rapamycin (mTOR) is a key regulatory kinase that integrates signals from Akt and other pathways to control cell growth, proliferation, and survival.

Apoptosis: The process of programmed cell death that is regulated by various signaling pathways, including those involving Akt, which can promote cell survival by inhibiting apoptotic factors.