PI3 kinase

PI3 Kinase (also known as Phosphoinositide 3-kinases or PI 3-kinases) are a family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which in turn are involved in cancer.

Function

PI3 Kinases are a family of related intracellular signal transducer enzymes capable of phosphorylating the 3 position hydroxyl group of the inositol ring of phosphatidylinositol (PtdIns). They are also known as phosphatidylinositol 3-kinases (PI 3-kinases or PI3Ks). The pathway, with oncogene PIK3CA and tumor suppressor PTEN (gene), is implicated in insensitivity of cancer tumors to insulin and IGF1, in calorie restriction.

Classification

PI 3-kinases have been classified into three classes based on their structure, regulation, and in vitro lipid substrate specificity.

• Class I PI 3-kinases are the most well studied and are activated by receptor tyrosine kinases, G protein-coupled receptors and Ras. They are heterodimeric, consisting of a catalytic (p110) and a regulatory subunit.
• Class II PI 3-kinases are less well characterized and are also activated by receptor tyrosine kinases, but appear to be regulated in a different manner.
• Class III PI 3-kinase is more similar to the yeast PI 3-kinase Vps34 and synthesizes Phosphatidylinositol 3-phosphate from Phosphatidylinositol in vivo.

Role in cancer

PI3K/AKT/mTOR pathway is an intracellular signaling pathway important in regulating the cell cycle. Therefore, it is directly related to cellular quiescence, proliferation, cancer, and longevity. PI3K activation phosphorylates and activates AKT, localizing it in the plasma membrane. AKT can have a number of downstream effects such as activating CREB, inhibiting p27, localizing FOXO in the cytoplasm, activating PtdIns-3ps, and activating mTOR which can affect transcription of p70 or 4EBP1.

See also

• Phosphoinositide 3-kinase inhibitor
• Phosphoinositide 3-kinase pathway
• Phosphoinositide 3-kinase-related kinase

References

PI3 kinase Resources
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