Phospholipases, other

Hydrolases. Enzymes catalysing the hydrolytic cleavage ofC —O, C —N and C —C bonds. The systematic name always includes hydrolase but the recommended name is often formed by the addition of ase to the substrate. Examples are esterases, glucosidases, peptidases, proteinases, phospholipases. Other bonds may be cleaved besides those cited, e.g. during the action of sulphatases and phosphatases. 

Phospholipases other than phospholipase C are also stimulated by G proteins. Arachidonic acid, released from phosphatidylcholine, is the major metabolic precursor to eicosanoids. Phospholipase A2, which releases fatty acids from glycerophospholipids, also interacts with G proteins, and phospholipase D (see here) is thought to participate in signal transduction via diacylglycerol formation. In addition, some phospholipases are controlled by Ca. ... 

The venoms of poisonous snakes contain (among other things) a class of enzymes known as phospholipases, enzymes that cause the breakdown of phospholipids. For example, the venoms of the eastern diamondback rattlesnake (Crotalus adamanteus) and the Indian cobra Naja naja) both contain phospholipase Ag, which catalyzes the hydrolysis of fatty acids at the C-2 position of glyc-erophospholipids. 

The second type of material includes spores, which may or may not produce disease symptoms but which can germinate in the insect gut and give rise to vegetative bacterial cells which in turn may produce, and exoenzymes such as phospholipases (lecithinases) or hyaluronidase. The phospholipases may produce direct toxic symptoms owing to their action on nervous or other phospholipid-containing tissue. Hyaluronidase breaks down hyaluronic acid and produces effects on animal tissue which are morphologically similar to the breakdown of insect gut wall in the presence of microbial insecticide preparations. 

PH domains consist of about 120 amino acid residues. They do not interact with other proteins, but associate with specific polyphosphoinositides. Consequently, PH domains appear to be important for localizing target proteins to the plasma membrane. Examples of PH domain-containing proteins include phospholipase C andpl20/RasGAP (Fig. 1). 

Two AR subtypes, Ax and A3, couple through G to inhibit adenylate cyclase, while the other two subtypes, A2a and A2B, stimulate adenylate cyclase through Gs or G0if (for A2a). The A2BAR is also coupled to the activation of PLC through Gq. Furthermore, each of these receptors may couple through the (3,y subunits of the G proteins to other effector systems, including ion channels and phospholipases. Levels of intracellular... 

Activation of Mi, M3, and M5 mAChRs does not only lead to the generation of IP3 followed by the mobilization of intracellular Ca2+, but also results in the stimulation of phospholipase A2, phospholipase D, and various tyrosine kinases. Similarly, M2 and M4 receptor activation does not only mediate the inhibition of adenylyl cyclase, but also induces other biochemical responses including augmentation of phospholipase A2 activity. Moreover, the stimulation of different mAChR subtypes is also linked to the activation of different classes of mitogen-activated protein kinases (MAP kinases), resulting in specific effects on gene expression and cell growth or differentiation. 

Hormonal factors and other stimuli by activating phospholipase C-(3 or -y isoforms stimulate the breakdown of phosphatidylinositol 4,5-bisphosphate to inositol 1,4,5-trisphosphate and diacylglycerol, a reaction called PI response. 

Among the substrates of Src are other nonreceptor PTKs (e.g., Fak, Syk, and Tec kinases), RTKs (e.g. EGF and PDGF receptors), phospholipase Cy, PI3-kinase, phosphatases (e.g., SHP-2 and PP2A), and adaptor (e.g., She and Cbl) as well as focal adhesion proteins (e.g., paxillin, pl30Cas andtensin). Src-mediated phosphorylation either modulates enzymatic activity of... 

Figure 10. The G-protein cascades in smooth muscle catalyze the exchange GDP for GTP on G-protein. Following the binding of GTP, the trimeric G-protein splits into an a-GTP part and a P-y part. The a-GTP part ordinarily then combines with its specific apoenzyme to constitute the active enzyme. For the activation of the contractile activation path, the enzyme is phospholipase C and the second messenger products are IP3 and DAG. The IP3 in the myoplasm binds to Ca channels in the SR membrane, opening them. Other second messengers include the inhibitors of contractile activity, cGMP and cAMP.

Ca may activate phospholipase A2 and cause production of lyso-lipids and fatty acids. In addition, ionic fluxes across the membrane occur, leading to pH changes and membrane depolarization. It is not clear how these other responses are initiated, but there may be direct G-protein links to effector systems such as phospholipase A2 or ionic channels. 

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