Class I PI 3-kinases

Class I PI 3-kinases

Class I PI 3-kinases (phosphoinositide 3-kinases) are a subgroup of the PI 3-kinase family of enzymes that play a crucial role in cellular functions such as growth, proliferation, differentiation, motility, survival, and intracellular trafficking. These enzymes are involved in the signaling pathways of many growth factors and hormones, making them critical to understanding various physiological and pathological processes.

Structure and Function

Class I PI 3-kinases are heterodimeric enzymes composed of a regulatory subunit and a catalytic subunit. They are divided into two subclasses: Class IA and Class IB.

Class IA PI 3-kinases

Class IA PI 3-kinases are activated by receptor tyrosine kinases (RTKs) and are composed of a p110 catalytic subunit (p110α, p110β, or p110δ) and a regulatory subunit (p85α, p85β, or p55γ). These enzymes primarily phosphorylate the 3' position of the inositol ring of phosphatidylinositol (4,5)-bisphosphate (PIP2) to generate phosphatidylinositol (3,4,5)-trisphosphate (PIP3), a second messenger involved in the activation of downstream signaling pathways such as the AKT pathway.

Class IB PI 3-kinases

Class IB PI 3-kinases are activated by G-protein-coupled receptors (GPCRs) and consist of a p110γ catalytic subunit and a p101 or p84 regulatory subunit. Similar to Class IA, they also produce PIP3, which is involved in various cellular responses.

Role in Disease

Class I PI 3-kinases are implicated in several diseases, including cancer, diabetes, and cardiovascular diseases. The PI3K/AKT/mTOR pathway, in particular, is frequently dysregulated in cancer, leading to increased cell survival and growth. Inhibitors targeting specific isoforms of PI 3-kinases are being developed as potential therapeutic agents.

Research and Therapeutic Implications

Research into Class I PI 3-kinases has led to the development of several inhibitors, some of which are in clinical trials or have been approved for use in certain cancers. These inhibitors aim to block the aberrant signaling pathways that contribute to tumor growth and survival.

Also see

• Phosphoinositide 3-kinase
• AKT signaling pathway
• mTOR pathway
• Receptor tyrosine kinase
• G-protein-coupled receptor