General Background : MYO-INOSITOL "myo-Inositol"-containing phospholipids play an important role in the control of cellular functions within eukaryotic cells, being part of the intracellular signal transductions pathways from various regulators, including hormones, neurotransmitters, growth factors, and serum . When these regulators interact with their receptors in cell membranes, they induce the hydrolysis of certain : Phosphoinositides "phosphoinositides" to produce second messenger molecules. A particularly important reaction is the cleavage of : PHOSPHATIDYL-MYO-INOSITOL-45-BISPHOSPHA "1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate", which produces two secondary messengers. One of the cleavage products, : INOSITOL-1-4-5-TRISPHOSPHATE, mobilizes : CA+2 ions from intracellular vesicular stores while the other product, : DIACYLGLYCEROL "1,2-diacyl-sn-glycerol", activates : HS07962-MONOMER "protein kinase C" , resulting in a variety of biochemical and pharmacological responses. The second messengers derived from inositol phospholipids are crucial for initiation of cellular activation, proliferation, differentiation and apoptosis. Variability in the sensitivity of individual receptors to : INOSITOL-1-4-5-TRISPHOSPHATE is a key factor that determines whether transient fluxes of : CA+2 release are destined to remain a localized phenomenon, or instead are recruited to produce calcium waves that sweep across the cell. About This Pathway : L-1-phosphatidyl-inositols "Phosphatidylinositol" is synthesized from : CDPDIACYLGLYCEROL "CDP-diacylglycerol" and : MYO-INOSITOL by phosphatidylinositol synthase. This compound can be phosphorylated by several kinases. In this pathway, it is converted by phosphatidylinositol 4-kinase enzymes to : CPD-1108 "phosphatidylinositol 4-phosphate", which is phosphorylated again by phosphatidylinositol-4-phosphate 5-kinases to form : PHOSPHATIDYL-MYO-INOSITOL-45-BISPHOSPHA "phosphatidylinositol 4,5-bisphosphate". Even though it has been shown that : PHOSPHATIDYL-MYO-INOSITOL-45-BISPHOSPHA "phosphatidylinositol 4,5-bisphosphate" is also synthesized from : 1-PHOSPHATIDYL-1D-MYO-INOSITOL-5-PHOSPHA "phosphatidylinositol 5-phosphate" , it is generally accepted that the majority of the : PHOSPHATIDYL-MYO-INOSITOL-45-BISPHOSPHA "phosphatidylinositol 4,5-bisphosphate" comes from : CPD-1108 "phosphatidylinositol 4-phosphate" phosphorylation . The last step in this pathway, which is the most important, is catalyzed by phospholipase C enzymes. These enzymes, acting in response to receptor activation, cleave : PHOSPHATIDYL-MYO-INOSITOL-45-BISPHOSPHA "phosphatidylinositol-4,5-bisphosphate" to : DIACYLGLYCEROL "1,2-diacylglycerol" (DAG) and : INOSITOL-1-4-5-TRISPHOSPHATE (IP3). The enzymes of this signal transduction pathway have many isoforms (not all of which are presented here) that are expressed in different tissues and under different circumstances. The presence of so many isoforms enables the transducton of multiple signals without interference in complex networks of signaling cascades that are not yet well understood . For example, humans have at least four isoforms of phosphatidylinositol 4-kinase, four isoforms of phosphatidylinositol-4-phosphate 5-kinase, and eleven isoforms of phospholipase C enzymes that belong to at least six distinct classes

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PI4KA , PI4KB , PIP4K2A , PLCB2 , PLCB3 , PLCD1 , PLCG1 , PLCG2 , PIP5K1A , PIP5K1B , PIP4K2B , CDIPT , PLCH1 , PIP5K1C , PLCE1 , TMEM216 , PI4K2B , PI4K2A , PIP4K2C , PLCD4 , PLCZ1 , PLCD3 , PIP5KL1 ,