description
: Phosphoinositides "Phosphoinositides" play a key role in signal transduction, transmitting signals from the cell surface to modulate intracellular processes. One well known phosphoinositide pathway produces the secondary messengers : INOSITOL-1-4-5-TRISPHOSPHATE and : DIACYLGLYCEROL "diacylglycerol" and is described in : PWY-6351. The 3-phosphoinositide pathway described here is another one of the major pathways of intracellular signal transduction. At the center of this pathway are the phosphatidylinositol 3-kinases (PI 3-kinases), enzymes that produce the monophosphate : CPD-177 "phosphatidylinositol 3-phosphate", the bisphosphate : 1-PHOSPHATIDYL-1D-MYO-INOSITOL-34-BISPH "phosphatidylinositol 3,4-bisphosphate" and the trisphosphate : PHOSPHATIDYLINOSITOL-345-TRIPHOSPHATE "phosphatidylinositol 3,4,5-trisphosphate", all important compounds in signaling cascades that influences a wide variety of cellular functions. The 3-phosphoinositide pathway has been implicated in growth factor-dependent mitogenesis, membrane ruffling and glucose uptake, cell proliferation, oncogenic transformation, cell survival, cell migration, and intracellular protein trafficking. . Some of the products of the PI 3-kinases, namely : 1-PHOSPHATIDYL-1D-MYO-INOSITOL-34-BISPH "phosphatidylinositol 3,4-bisphosphate" and the trisphosphate : PHOSPHATIDYLINOSITOL-345-TRIPHOSPHATE "phosphatidylinositol 3,4,5-trisphosphate", are almost absent in quiescent cells but are produced rapidly upon stimulation by a variety of factors, suggesting a likely function as second messengers. In addition, these compounds do not seem to be substrates for phospholipases C , and it has been proposed that they may act via the activation of certain protein kinases such as Akt/RAC/PKB and certain protein kinase C isoforms . The enzymes responsible for the generation of 3' phosphoinositides, phosphatidylinositol 3-kinases, have been assigned to three classes based on structural similarity, substrate specificity, and probable mechanism of activation . Class I is composed of heterodimeric enzymes, each containing one catalytic subunit, encoded by : HS04527, : HS00644, : HS02818 or : HS10353, and one regulatory subunit, encoded by : HS07270, : HS02779, : HS04135, : HS13887 or : HS16294. Even though all class I enzymes can phosphorylate in vitro :L-1-phosphatidyl-inositols "phosphatidylinositol", : CPD-1108 and : PHOSPHATIDYL-MYO-INOSITOL-45-BISPHOSPHA, only the later is beleived to be the in vivo substrate (:2.7.1.153-RXN "EC 2.7.1.153"). Class II enzymes are monomeric proteins that are distinguished by a carboxy-terminal C2 (CalB) : CA+2-binding domain , and are encoded by : HS00315, : HS05725 and : HS06583. They accept several types of substrates, and are the only mammalian enzyme thought to catalyze :2.7.1.154-RXN "EC 2.7.1.154". Class III enzymes are heterodimeric, composed of a catalytic subunit (: HS01275) and a regulatory subunit (: HS03788). These enzymes, which are homologs of the yeast Vps34p protein, can only phosphorylate :L-1-phosphatidyl-inositols (: 1-PHOSPHATIDYLINOSITOL-3-KINASE-RXN "EC 2.7.1.137")

external resources
NCBI:545314
BIOCYC:HUMAN_PWY-6352
PUBMED:9632630
PUBMED:7798235
PUBMED:2553693
PUBMED:8086005
PUBMED:9247130

genes
PIK3C2A , PIK3C2B , PIK3C2G , PIK3C3 , PIK3CA , PIK3CB , PIK3CD , PIK3CG , PIK3R1 , PIK3R2 , PI4KA , PI4KB , PIP5K1A , PIP5K1B , PIP4K2B , PIK3R3 , FIG4 , CDIPT , SACM1L , PIP5K1C , PIK3R5 , PIK3R4 , PI4K2B , PI4K2A , PIP5KL1 , PIK3R6 , PIKFYVE ,