Phospholipase isoforms

Phospholipase D is widely distributed in bacteria, fungi, plants and animals, and is present in almost all mammalian cells [3]. In mammals, it occurs as alternatively spliced products of two genes (PLD1 andPLD2) (Fig. 3). Most mammalian cells express different levels of both isoforms. Both PLD1 and PLD2 have four conserved sequences (I-IV), and sequences I and IV contain the HXKX4D (HKD) motif that is characteristic of the PLD superfamily, which includes bacterial endonucleases, phospholipid synthases, viral envelope... 

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. 

FRET probes have not only been generated to measure the phospholipase activity but to study its substrate specificity as well. Several substrates of PLA2 with a variety of head groups and labeled with a BODIPY dye and a Dabcyl quencher were created by Rose et al. and tested against different PLAs in cells to determine substrate specificity and intracellular localization [137], The specificity of PLA2 isoforms towards the number of double bonds in the sn2 position was evaluated with a small series of PENN derivatives. It was demonstrated that the cytosolic type V PLA2 preferred substrates with a single double bond [138],... 

Fiucci G, Czarny M, Lavie Y, Zhao D, Berse B, Blusztajn JK, Liscovitch M (2000) Changes in phospholipase D isoform activity and expression in multidrug-resistant human cancer cells. Int J Cancer 85 882-888... 

The pleckstrin homology (PH) domain is a structural motif of ca. 100 amino acids foimd in many signal molecules such as Ser/Thr-specific protein kinases, tyrosine kinases, isoforms of phospholipase C (PL-CP, y and 6), in G nucleotide exchange factors, adaptor proteins, and in proteins of the cytoskeleton (see also Fig. 8.10). Originally, the PH domain was foimd in the 47 kDa pleckstrin protein, which is the main substrate of protein kinase C in platelets. 

Prostanoid receptors and their signaling pathways. fMLP, formylated MetLeuPhe, a small peptide receptor PLC-3, phospholipase C-3. All of the receptors shown are of the 7-transmembrane, G-protein coupled type. The terms "relaxant," "contractile," and "inhibitory" refer to the phylogenetic characterization of their primary effects. AII EP3 isoforms couple through G but some can also activate Gs or G12/13 pathways. RhoGEF, rho guanine nucleotide exchange factor. See text for additional details. 

Subtypes are described for PGE2 receptors (EPi, EP2, EP3, and EP4), each of which activates distinct signaling pathways. EPi is coupled to activation of phospholipase C, EP2 and EP4 to stimulation of adenylyl cyclase. EP3 appears to have multiple effects depending on concentration. The recent description of isoforms of receptor subtypes with coupling to different G proteins makes the issue of second messenger activation more complex. However this multiplicity of pathways may help clarify seemingly paradoxical experimental results. 

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