Taxonomic distribution of proteins containing PI3Kc domains

The PI3Kc domain within your query sequence starts at position and ends at position , and its E-value is < 1e-12.

Phosphatidylinositol phosphate kinases, a multifaceted family of signaling enzymes.

Anderson RA, Boronenkov IV, Doughman SD, Kunz J, Loijens JC
J Biol Chem. 1999; 274: 9907-10

Structural insights into phosphoinositide 3-kinase catalysis and signalling.

Walker EH, Perisic O, Ried C, Stephens L, Williams RL
Nature. 1999; 402: 313-20

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.

Regulation of inositol lipid kinases by Rho and Rac.

Ren XD, Schwartz MA
Curr Opin Genet Dev. 1998; 8: 63-7

Rho and Rac small GTPases associate with type-I phosphatidylinositol 4-phosphate 5-kinase to regulate the production of phosphatidylinositol 4,5-bisphosphate. This lipid appears to mediate some of the effects of Rho and Rac on the actin cytoskeleton. The genes for several type-I phosphatidylinositol 4-phosphate 5-kinases have been cloned recently but it is not known which one interacts with Rho and/or Rac. Rho family GTPases also interact with phosphatidylinositol 3-kinase, though this kinase can be either upstream or downstream of the GTPases depending upon the system.

Using structure to define the function of phosphoinositide 3-kinase family members.

Domin J, Waterfield MD
FEBS Lett. 1997; 410: 91-5

Signalling through the lipid products of phosphoinositide-3-OH kinase.

Toker A, Cantley LC
Nature. 1997; 387: 673-6

When a stimulatory agonist molecule binds at the exterior of the cell membrane, a second messenger transduces the signal to the interior of the cell. Second messengers can be derived from phospholipids in the membrane by the action of the enzymes phospholipase C or phosphoinositide-3-OH kinase (PI(3)K). PI(3)K is a key player in many cellular responses, including the movement of organelle membranes, shape alteration through rearrangement of cytoskeletal actin, transformation and chemotaxis. But how PI(3)K mediates these responses is only now becoming clear.

Phosphoinositide 3-kinases: a conserved family of signal transducers.

Vanhaesebroeck B, Leevers SJ, Panayotou G, Waterfield MD
Trends Biochem Sci. 1997; 22: 267-72

Phosphoinositide 3-kinases (PI3Ks) generate lipids that are implicated in receptor-stimulated signalling and in the regulation of membrane traffic. Several distinct classes of PI3Ks have now been identified that have been conserved throughout eukaryotic evolution. Potential signalling pathways downstream of PI3Ks have been elucidated and PI3K function is now being characterised in several model organisms.

Phosphoinositide kinases.

Carpenter CL, Cantley LC
Curr Opin Cell Biol. 1996; 8: 153-8

Recently, a number of cDNA clones with homology to the catalytic subunit of phosphoinositide 3-kinase have been identified, and the sequence of the first cDNA clone encoding a phosphatidylinositol 4-phosphate 5-kinase has been published. Use of both dominant-negative mutants of phosphoinositide 3-kinase and the inhibitors wortmannin and LY294002 has identified a number of processes in which phosphoinositide 3-kinase participates, including cell motility, the Ras pathway, vesicle trafficking and secretion, and apoptosis. Several possible biochemical targets of phosphoinositides have been found.

PIK-related kinases: DNA repair, recombination, and cell cycle checkpoints.

Keith CT, Schreiber SL
Science. 1995; 270: 50-1

Relationship of the ataxia-telangiectasia protein ATM to phosphoinositide 3-kinase.

Lavin MF, Khanna KK, Beamish H, Spring K, Watters D, Shiloh Y
Trends Biochem Sci. 1995; 20: 382-3

Phosphatidylinositol 3-kinase.

Kapeller R, Cantley LC
Bioessays. 1994; 16: 565-76

Currently, a central question in biology is how signals from the cell surface modulate intracellular processes. In recent years phosphoinositides have been shown to play a key role in signal transduction. Two phosphoinositide pathways have been characterized, to date. In the canonical phosphoinositide turnover pathway, activation of phosphatidylinositol-specific phospholipase C results in the hydrolysis of phosphatidylinositol 4,5-bisphosphate and the generation of two second messengers, inositol 1,4,5-trisphosphate and diacylglycerol. The 3-phosphoinositide pathway involves protein-tyrosine kinase-mediated recruitment and activation of phosphatidylinositol 3-kinase, resulting in the production of phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate. The 3-phosphoinositides are not substrates of any known phospholipase C, are not components of the canonical phosphoinositide turnover pathway, and may themselves act as intracellular mediators. The 3-phosphoinositide pathway has been implicated in growth factor-dependent mitogenesis, membrane ruffling and glucose uptake. Furthermore the homology of the yeast vps34 with the mammalian phosphatidylinositol 3-kinase has suggested a role for this pathway in vesicular trafficking. In this review the different mechanisms employed by protein-tyrosine kinases to activate phosphatidylinositol 3-kinase, and its involvement in the signaling cascade initiated by tyrosine phosphorylation, are examined.