Phospholipase Regulation

Phospholipase, regulated by integrins and growth factors though tyrosine phosphorylation... 

The eicosanoids are locally active hormones (autocoids) that are derived from precursor polyunsaturated fatty acids. The rate-limiting step in the synthesis of eicosanoids is the phospholipase-regulated release of arachidonic add from membranes. Arachi-donic acid metabolism may follow one of three possible pathways. In the first, the cydooxygenase- peroxidase pathway leads to the formation of the prostenoids - prostaglandins and thromboxanes. In the second, the lipoxygenase pathway yields the leuko-trienes and lipoxins. A third pathway, the cytochrome P-450 mono oxygenase pathway is also involved in the metabolism of arachidonic add. 

Rhee SG, Bae YS (1997) Regulation of phosphoinositide-specific phospholipase Isozymes. J Biol Chem 272 15045-15048... 

Exton JH (2002) Phospholipase D - structure, regulation and function. Rev Physiol Biochem Pharmacol 144 1-94... 

A subfamily of Rho proteins, the Rnd family of small GTPases, are always GTP-bound and seem to be regulated by expression and localization rather than by nucleotide exchange and hydrolysis. Many Rho GTPase effectors have been identified, including protein and lipid kinases, phospholipase D and numerous adaptor proteins. One of the best characterized effector of RhoA is Rho kinase, which phosphorylates and inactivates myosin phosphatase thereby RhoA causes activation of actomyosin complexes. Rho proteins are preferred targets of bacterial protein toxins ( bacterial toxins). 

Covalent regulation. Following occupation and activation of the M2 acetyl choline receptors, phospholipase C (PLC), is activated and both inositol (l,4,5)-trisphosphate (IP3), and diacylglycerol (DAG), are formed by hydrolysis of phosphatidylinositol (4,5)-bisphosphate (PIP2). 

Schaefer U, Schneider A, Rixen D, Neugebauer E (1998) Neutrophil adhesion to histamine stimulated cultured endothelial cells is primarily mediated via activation of phospholipase C and nitric oxide synthase isozymes. Inflamm Res 47(6) 256-264 Schaefer U, Schmitz V, Schneider A, Neugebauer E (1999) Histamine induced homologous and heterologous regulation of histamine receptor subtype mRNA expression in cultured endothelial ceUs. Shock 12(4) 309-315... 

Histamine Hi, Hj Hz G, Gs Phospholipase-C to IPzto [Ca +]i regulation Stimulates adenylyl cyclase raising cAMP... 

Dopamine Di Dz, D4 D3 Gs Go, Gi G, Stimulates adenylyl cyclase raising cAMP Inhibits adenylyl cyclase, Ca +/K+ channels Phospholipase-C to IPsto [Ca +]i regulation... 

Glutamate-metabotropic mGluRl, 3, 5 mGluR2, 4, 6, 7 G, Go, Gi Phospholipase-C to IP3 to [Ca +]i regulation Inhibits adenylyl cyclase, Ca /K channels... 

Free radicals are by-products of prostaglandin metabolism and may even regulate the activity of the arachidonate pathway. Arachidonic acid, released from lipids as a result of activation of phospholipases by tissue injury or by hormones, may be metabolized by the prostaglandin or leu-kotriene pathways. The peroxidase-catalysed conversion of prostaglandin G2 to prostaglandin H2 (unstable prostanoids) and the mechanism of hydroperoxy fatty acid to the hydroxy fatty acid conversion both yield oxygen radicals, which can be detected by e.s.r. (Rice-Evans et al., 1991). 

Smit MJ, Verdijk P, van der Raaij-Helmer EM, et al. CXCR3-mediated chemotaxis of human T cells is regulated by a Gi- and phospholipase C-dependent pathway and not via activation of MEK/p44/p42 MAPK nor Akt/PI-3 kinase. Blood 2003 102(6) 1959-1965. 

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