Protein kinase B

Content sourced from Wikipedia, licensed under CC BY-SA 3.0.

Protein kinase B (PKB), also known as Akt, is a family of three enzymes: Akt1, Akt2, and Akt3. They are serine/threonine kinases that help control glucose use, cell survival, growth, gene expression, and cell movement.

How Akt works
- Each Akt has a pleckstrin homology (PH) domain that binds membrane lipids PIP3 or PIP2.
- When growth signals activate PI3K, PIP3 builds up at the membrane and recruits Akt.
- Akt is activated by two other kinases: PDPK1 (at threonine 308 in Akt1) and mTORC2 (at serine 473 in Akt1).
- Once active, Akt adds phosphate groups to many targets, promoting survival and growth. Examples include BAD (prevents apoptosis), GSK-3 (controls glycogen production), mTOR (protein synthesis), NF-κB, MDM2, and TFEB (lysosome biogenesis). Akt also helps move glucose transporters (GLUT4) to the cell surface.

Isoforms and their roles
- Akt1: supports cell survival, growth, and development; involved in blood vessel formation and other growth processes.
- Akt2: important for insulin signaling and glucose uptake; affects growth as well.
- Akt3: mainly expressed in the brain.

Regulation and disease
- PTEN removes PIP3, turning off the signal. SHIP and the phosphatases PHLPP1/2 also help shut Akt down.
- Aberrant Akt activity is common in many cancers, where it helps tumor cells survive and grow. Because of its central role, Akt is a target for cancer drugs. Several inhibitors have been tested in trials, including MK-2206, ipatasertib, AZD5363, and perifosine.

Other notes
- Akt activity can influence processes beyond cancer, such as brain development and blood vessel formation, and its interaction with other factors can have complex effects in different diseases.

In short, Akt acts as a central signaling hub that connects growth signals to decisions about cell survival, growth, and metabolism.