Phospholipase Subfamilies

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). 

The first members of the Gi subfamily to be discovered displayed an inhibitory effect on adenylyl cyclase, thus the name Gi, for inhibitory G-proteins. Further members of the Gi subfamily have phospholipase C as the corresponding effector molecule. Signal transmission via phospholipase C flows into the inositol triphosphate and diacylglyce-rol pathways (see Chapter 6). 

The members of the G, subfamily are not modifiable by pertussis toxin or cholera toxin. The signal protein next in the reaction sequence is generally the P-type of phospholipase C. 

Murakami, M., Kambe, T., Shimbara, S., Higashino, K., Hanasaki, K., Arita, H., Horiguchi, M., Arita, M., Arai, H., Inoue, K. and Kudo, I., 1999, Different functional aspects ofthe group II subfamily (Types IIA and V) and type X secretory phospholipase A(2)s in regulating arachidonic add release and prostaglandin generation. Implications of cyclooxygenase-2 induction and phospholipid scramblase-mediated cellular membrane perturbation../. Biol. Chem., 274 31435-31444. 

Figure 4. Linear representation of the Arabidopsis PIPKs and PLCs. The Arabidopsis PtdlnsP 5-kinases are most similar to the human type I PtdlnsP 5-kinases. There are 11 putative type I /I/PtdlnsP 5-kinases in Arabidopsis arranged in two subfamilies based on size. Subfamily B contains X/PIPK1-9, all of which contain membrane occupation and recognition nexus (MORN) repeats. /1/PIPK10-11 are in Subfamily A with molecular weights less than that of the members of subfamily B and contain no MORN repeats. The Arabidopsis phosphoinositide specific phospholipase C family is most similar to the animal PLC . There are seven functional PI-PLCs in Arabidopisis (Hunt et al., 2004). All isoforms contain EF-hand motifs, the X and Y catalytic domains characteristic of PI-PLCs and a C2 lipid-binding domain.

The mannose receptor subfamily is a group of membrane-attached C-type lectins with multiple CRDs. Since most of these domains maintain neither calcium-binding nor sugarbinding properties, the term C-type lectin-like domain (CTLD) is more frequently used lately instead of the term CRD. The mannose receptor subfamily comprises four members including the mannose receptor, the M-type phospholipase A2... 

It has now been established by studies of numerous tissues that the interaction of all members of the Nk receptor family with appropriate ligands results in G protein-linked activation of phospholipase C and phos-phoinositol turnover with increased synthesis of inositol triphosphate (IPs) and consequent increases in levels of intracellular calcium (Nakanishi et al., 1993). This activation occurs via a pertussis toxin-insensitive pathway and probably involves the Gq/11 subfamily of Ga proteins (Kwatra et al., 1993). Activation of transfected tachykinin receptors in CHO cells can also result in the generation of cAMP (Nakajima et al., 1992 Wiener, 1993). 

Rac proteins (Racl,2), which are also members of the Rho subfamily, are involved in membrane ruffling and lamellipodia formation induced by growth factors (Ridley et al., 1992 Hall, 1994), and it has also been suggested that they are important for Ras-induced transformation (Qiu et al., 1995). Moreover, Rac proteins control NADPH oxidase (Abo et al., 1991 Bokoch, 1994), and may have a role in phospholipase A2 regulation (Peppelenbosch et al., 1995). Cdc42, another member of the Rho family, which occurs in at least two iso-... 

Although the phospholipases of type Cfi and Cy catalyze the same biochemical reaction, they are activated via different signaling pathways. The Cfi subfamily participates in G protein signaling while the members of the Cy subfamily function as effectors of receptor tyrosine kinases (see Chapter 8). 

Other possible Rho effectors—atypical PKC and phosphatidylinositol-4-phosphate 5-kinase The protein kinase C family of ser/thr kinases is divided into three subfamilies, classical, novel, and atypical, with each class containing several isozymes. Classical PKCs are activated by Ca + and diacylglycerol and thus are typically activated downstream of phospholipase C activation. Novel PKCs are activated by diacylglycerol, and atypical PKCs are not activated by Ca or diacylglycerol and thus are not downstream of PLC [414]. Neutrophils contain classical isozymes a, Pj, and Pn, novel isozyme 8, and atypcial isozyme, [174, 200]. 

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