Phosphatidylinositol 3-kinase, Vps34 type

Phosphatidylinositol 3-kinase, Vps34 type(InterPro Protein Domain record)

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Phosphatidylinositol 3-kinase, Vps34 type

InterPro Protein Domain record

description http://metadb.riken.jp/db/SciNetS_rib124i/prib124u1i

Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyse the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyse the reverse process. Protein kinases fall into three broad classes, characterised with respect to substrate specificity [<cite idref="PUB00005115"/>]: <ul> <li>Serine/threonine-protein kinases</li><li>Tyrosine-protein kinases</li><li>Dual specific protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins)</li> </ul> Protein kinase function has been evolutionarily conserved from <taxon tax_id="562">Escherichia coli</taxon> to human [<cite idref="PUB00020114"/>]. Protein kinases play a role in a multitude of cellular processes, including division, proliferation, apoptosis, and differentiation [<cite idref="PUB00015362"/>]. Phosphorylation usually results in a functional change of the target protein by changing enzyme activity, cellular location, or association with other proteins. The catalytic subunits of protein kinases are highly conserved, and several structures have been solved [<cite idref="PUB00034898"/>], leading to large screens to develop kinase-specific inhibitors for the treatments of a number of diseases [<cite idref="PUB00034899"/>].Members of this family are Class III phosphatidylinositol 3-kinases (PI3Ks) (catalytic subunits). PI3K is a lipid kinase and a key signalling enzyme involving in cell survival and proliferation, cell motility and adhesion, cytoskeletal rearrangement and vesicle trafficking [<cite idref="PUB00011140"/>]. The different PI3K isoforms have cell-specific functions. In yeast, VPS34 is a key enzyme required for cell division, vacuolar protein sorting, and vacuole segregation [<cite idref="PUB00005166"/>]. The major components of the yeast VPS intracellular trafficking complex are conserved in humans [<cite idref="PUB00011141"/>]. There are three major classes of PI3Ks, I and III (Class I is also subdivided into Ia and Ib), and a more distantly relatedClass IV which contains Ser/Thr kinases. The different classes of PI3K catalyse phosphorylation of the 3'-OH position of phosphatidyl myo-inositol (PtdIns) lipids, generating different 3'-phosphorylated lipid products that act as secondary messengers. The classification of PI3Ks is based upon sequence analysis and domain architecture of the catalytic subunits, but the divisions also reflect the biochemical properties and the differential association with a variety of regulatory adaptor subunits. This division is mirrored not only in their specialised functions but also in the different modes of regulation of the different enzymes in the family [<cite idref="PUB00007087"/>]. Furthermore, each of the PI3K classes differ in their preferred lipid substrate. Class III PI3Ks use only phosphatidylinositol as substrate, whereas Class Ia and Ib PI3K activity is focused upon phosphatidylinositol (4,5)-bisphosphate as substrate in vivo [<cite idref="PUB00007087"/>]. These substrate-related differences are presumed to result from subtle variations in the structures of the active sites of the different PI3Ks. Class III PI3Ks contain only the core catalytic subunit, which consists of the N-terminal C2 domain, the helical domain and the double-lobed catalytic domain. Class I and II contain an additional Ras-binding domain. The N-terminal C2 domain interacts mainly with the scaffolding helical domain of the enzyme [<cite idref="PUB00007087"/>]. The function of the central helical domain is not clear, it has been suggested to be involved in substrate presentation [<cite idref="PUB00001709"/>]. The C-terminal catalytic domain is shared by the PI3- and PI4-kinases. This domain is distantly related to the catalytic domain of protein kinases, with a global similarity of the core topological features but significantdifferences in the substrate-binding sites [<cite idref="PUB00007087"/>]. For additional information please see [<cite idref="PUB00011142"/>].

label http://www.w3.org/2000/01/rdf-schema#label