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Phosphoinositide 3-kinases

Phosphatidylinositol-4,5-bisphosphate 3-kinase
PI3kinase.png
PIK-93 inhibitor (yellow) bound to the PI3 Kinase 110 gamma subunit .
Identifiers
Symbol PIK3
Pfam PF00454
InterPro IPR000403
SMART SM00146
PROSITE PDOC00710
SCOP 3gmm
SUPERFAMILY 3gmm
OPM superfamily 302
OPM protein 3ml9
Phosphoinositide 3-kinase
Identifiers
EC number 2.7.1.137
CAS number 115926-52-8
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum

Phosphatidylinositol-4,5-bisphosphate 3-kinase (also called phosphatidylinositide 3-kinases, phosphatidylinositol-3-kinases, PI 3-kinases, PI(3)Ks, PI-3Ks or by the HUGO official stem symbol for the gene family, PI3K(s)) 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.

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

The discovery of PI 3-kinases by Lewis Cantley and colleagues began with their identification of a previously unknown phosphoinositide kinase associated with the polyoma middle T protein. They observed unique substrate specificity and chromatographic properties of the products of the lipid kinase, leading to the discovery that this phosphoinositide kinase had the unprecedented ability to phosphorylate phosphoinositides on the 3' position of the inositol ring. Subsequently, Cantley and colleagues demonstrated that in vivo the enzyme prefers PtdIns(4,5)P2 as a substrate, producing the novel phosphoinositide PtdIns(3,4,5)P3.

The phosphoinositol-3-kinase family is divided into four different classes: Class I, Class II, Class III, and Class IV. The classifications are based on primary structure, regulation, and in vitro lipid substrate specificity.


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Wikipedia

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