Phosphoinositide 3-kinases (PI 3-kinases or PI3Ks) are a family of related enzymes that are capable of phosphorylating the 3 position hydroxyl group of the inositol ring of phosphatidylinositol (PtdIns). They are also known as phosphatidylinositol-3-kinases.
The majority of the research on PI 3-kinases has focused on the Class I PI 3-kinases. Class I PI 3-kinases are composed of a catalytic subunit known as p110 and a regulatory subunit either related to p85 or p101. The p85 subunits contain SH2 and SH3 domains ().
Class II comprises three catalytic isoforms (C2α, C2β, and C2γ), but unlike Classes I and III, no regulatory proteins. These enzymes catalyse the production of PI(3)P from PI (may also produce PI(3,4)P2 from PI(4)P), however little is known about their role in immune cells. C2α and C2β are expressed through the body, however expression of C2γ is limited to hepatocytes. The distinct feature of Class II PI3Ks is the C-terminal C2 domain. This domain lacks critical Asp residues to coordinate binding of Ca2+, which suggests class II PI3Ks bind lipids in a Ca2+ independent manner.
Class III are similar to II in that they bias the production of PI(3)P from PI, but are more similar to Class I in structure, as they exist as a heterodimers of a catalytic (Vps34) and a regulatory (p150) subunits. Class III seems to be primarily involved in the trafficking of proteins and vesicles. There is, however, evidence that they are able to contribute to the effectiveness of several process important to immune cells, not least phagocytosis.
AKT is activated as a result of PI3-kinase activity, because AKT requires the formation of the PtdIns(3,4,5)P3 (or "PIP3") molecule in order to be translocated to the cell membrane. At PIP3, AKT is then phosphorylated by another kinase called phosphoinositide dependent kinase 1 (PDK1), and is thereby activated. (Please do not confuse with the Pyruvate dehydrogenase kinase, isozyme 1 which is also abbreviated as PDK1). The "PI3-k/AKT" signaling pathway has been shown to be required for an extremely diverse array of cellular activities - most notably cellular proliferation and survival.
In addition to AKT and PDK1, one other related serine threonine kinase is bound at the PIP3 molecule created as a result of PI3-kinase activity, SGK.
In addition to the class I – class III PI 3-kinases there is a group of more distantly related enzymes that are sometimes referred to as class IV PI 3-kinases. The class IV PI 3-kinases family is composed of ataxia telangiectasia mutated (ATM), ataxia telangiectasia and Rad3 related (ATR), DNA-dependent protein kinase (DNA-PK) and mammalian Target Of Rapamycin (mTOR). These members of the PI 3-kinase superfamily are protein serine/threonine kinases.
Publication No. WO/2010/080996 Published on July 15, Assigned to Curis for Phosphoinositide 3-Kinase Inhibitor (American Inventors)
Jul 16, 2010; GENEVA, July 19 -- Xiong Cai, Haixiao Zhai, Cheng-Jung Lai and Changgeng Qian, all from the U. S., have developed...
Wipo Publishes Patent of Curis, Xiong Cai, Haixiao Zhai, Chengjung Lai, Changgeng Qian, Rudi Bao for "Phosphoinositide 3-Kinase Inhibitor with a Zinc Binding Moiety" (American Inventors)
Oct 05, 2012; GENEVA, Oct. 5 -- Publication No. WO/2012/135571 was published on Oct. 4. Title of the invention: "PHOSPHOINOSITIDE 3-KINASE...