activation of protein kinase B activity

Definition

Target type: biologicalprocess

Any process that initiates the activity of the inactive enzyme protein kinase B. [GOC:pg]

Protein kinase B (PKB), also known as AKT, is a serine/threonine-specific protein kinase that plays a crucial role in various cellular processes, including cell survival, growth, metabolism, and angiogenesis. Activation of PKB involves a complex signaling cascade initiated by growth factors, hormones, and other stimuli. The process can be summarized in the following steps:

1. **Ligand Binding and Receptor Activation:** The activation of PKB begins with the binding of a ligand, such as insulin or growth factors, to its specific receptor tyrosine kinase (RTK) on the cell surface. This binding event triggers a conformational change in the receptor, leading to its autophosphorylation on tyrosine residues.
2. **Recruitment of Adapter Proteins:** Phosphorylated tyrosine residues on the activated RTK serve as docking sites for adapter proteins, such as growth factor receptor-bound protein 2 (GRB2) and son of sevenless (SOS). GRB2 interacts with SOS through its SH2 domain, which binds to phosphorylated tyrosine residues.
3. **Activation of Ras:** SOS is a guanine nucleotide exchange factor (GEF) that activates Ras, a small GTPase. SOS facilitates the exchange of GDP for GTP on Ras, thereby activating it.
4. **Activation of Phosphoinositide 3-Kinase (PI3K):** Activated Ras recruits and activates PI3K, a lipid kinase. PI3K phosphorylates phosphatidylinositol-4,5-bisphosphate (PIP2) at the plasma membrane, converting it to phosphatidylinositol-3,4,5-trisphosphate (PIP3).
5. **Recruitment of PKB to the Plasma Membrane:** PIP3 serves as a docking site for PKB, which contains a pleckstrin homology (PH) domain that binds to PIP3. This interaction recruits PKB to the plasma membrane, bringing it close to its upstream activators.
6. **Phosphorylation of PKB by Phosphoinositide-Dependent Kinase 1 (PDK1):** Once at the plasma membrane, PKB is phosphorylated at Thr308 by PDK1, another kinase. This phosphorylation event is essential for PKB activation.
7. **Phosphorylation of PKB by Mammalian Target of Rapamycin Complex 2 (mTORC2):** In addition to Thr308 phosphorylation, PKB requires phosphorylation at Ser473 for full activation. This phosphorylation is catalyzed by mTORC2, a protein complex that is activated by growth factors and other stimuli.
8. **PKB Activation and Signaling:** Once fully phosphorylated at Thr308 and Ser473, PKB becomes fully active. It then phosphorylates a wide range of downstream targets, including glycogen synthase kinase 3 (GSK3), forkhead box O (FOXO) transcription factors, and the tuberous sclerosis complex (TSC2), leading to the regulation of various cellular processes.

The activation of PKB is a tightly regulated process, with multiple levels of control. Dysregulation of PKB signaling has been implicated in several diseases, including cancer, diabetes, and neurodegenerative disorders.'
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Proteins (9)

Compounds (572)