Diacylglycerol second messenger

Protein kinase C is activated by the second messenger diacylglycerol 356... 

Phosphatidylcholine (lecithin) is the most abundant phospholipid in membranes. Phosphatidylethanolamine (cephalin) has an ethanolamine residue instead of choline, and phosphatidylserine has a serine residue. In phosphatidylinositol, phosphatidate is esterified with the sugarlike cyclic polyalcohol myo-inositol. A doubly phosphorylated derivative of this phospholipid, phosphatidylinositol 4,5-bisphosphate, is a special component of membranes, which, by enzymatic cleavage, can give rise to two second messengers, diacylglycerol (DAG) and inositol l,4,5trisphosphate (InsPsi see p.386). 

Phosphatidylinositol-4,5-bisphosphate (PIP2) and the two second messengers, diacylglycerol and inositol trisphosphate, that are derived from it. 

The best known receptors for phorbol esters and their derivatives are the isozymes of protein kinase C (PKC), which bind phorbol esters and the physiological second messenger diacylglycerol (DAG) by cysteine-rich domains, the Cl domains. The exact functions of the different PKC isozymes is not known at present however, they have been shown to be involved in synaptic transmissions, the activation of ion fluxes, secretion, cell cycle control, differentiation, proliferation, tumorigenesis, metastasis, and apoptosis. 

Phospholipase C cleaves the membrane lipid phosphatidyl inositol 4,5-bisphosphate into two second messengers diacylglycerol, which remains in the membrane, and inositol 1.4,5-trisphosphate, which diffuses away from the membrane. 

Competition experiments have clearly shown that the second messenger diacylglycerol binds to the phorbol ester-binding site on the cysteine-rich domains in the Cl... 

Although knowledge of subcellular distribution is still incomplete, it seems that I, receptors are limited to cell membranes (Piletz et al., 1991 Ernsberger et al., 1995) and, at least in some preparations, are possibly coupled to G proteins, while L receptors are primarily localized in mitochondria and associated with monoamino oxidases (Tesson et al., 1995). In addition, a recent study (Ems-berger et al., 1997) has shown that activation of I, receptors in PC 12 cells leads to the production of the second messenger diacylglycerol. 

Certain heptahelical receptors bind the q isoform of the Ga subunit (Ga ), which activates the target enzyme phospholipase Cp (see Fig. 11.12). When activated, phospholipase Cp hydrolyzes the membrane lipid phosphatidyl inositol bis phosphate (PI-4,5-bisP) into two second messengers, diacylglycerol (DAG) and... 

Muscarinic mechanism Several molecular mechanisms of muscarinic action have been defined (Table 7-3). One involves G protein coupling of muscarinic receptors (especially M and Mj receptors) to phospholipase C, a membrane-bound enzyme, leading to the release of the second messengers diacylglycerol (DAG) and inositol-1,4,5-trisphosphate (IP3). DAG modulates the action of protein kinase C, an enzyme important in secretion, while IP3 evokes the release of calcium from intracellular storage sites, which results in contraction. A second mechanism couples muscarinic receptors (especially receptors) to adenylyl... 

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