Structural insights into phosphoinositide 3-kinase catalysis and signalling.

Article Details


Walker EH, Perisic O, Ried C, Stephens L, Williams RL

Structural insights into phosphoinositide 3-kinase catalysis and signalling.

Nature. 1999 Nov 18;402(6759):313-20.

PubMed ID
10580505 [ View in PubMed

Phosphoinositide 3-kinases (PI3Ks) are ubiquitous lipid kinases that function both as signal transducers downstream of cell-surface receptors and in constitutive intracellular membrane and protein trafficking pathways. All PI3Ks are dual-specificity enzymes with a lipid kinase activity which phosphorylates phosphoinositides at the 3-hydroxyl, and a protein kinase activity. The products of PI3K-catalysed reactions, phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3), PtdIns(3,4)P2 and PtdIns(3)P, are second messengers in a variety of signal transduction pathways, including those essential to cell proliferation, adhesion, survival, cytoskeletal rearrangement and vesicle trafficking. Here we report the 2.2 A X-ray crystallographic structure of the catalytic subunit of PI3Kgamma, the class I enzyme that is activated by heterotrimeric G-protein betagamma subunits and Ras. PI3Kgamma has a modular organization centred around a helical-domain spine, with C2 and catalytic domains positioned to interact with phospholipid membranes, and a Ras-binding domain placed against the catalytic domain where it could drive allosteric activation of the enzyme.

DrugBank Data that Cites this Article

NameUniProt ID
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoformP48736Details