Phosphoinositides Phospholipases

Drbak, B.K., Watkins, P.A.C., Valenta, R., Dove, S.K., Lloyd, C.W., Staiger, C.J., 1994, Inhibition of plant plasma membrane phosphoinositide phospholipase C by the actin-binding protein, profilin. Plant J. 6 389—400. 

BANNO Y, NAKASHIMA T, KUMADA T, EBISAWA K, NONOMURA Y, NOZAWA Y. Effects of gdsolin ai human platdd cytosolic phosphoinositide-phospholipase C isoqrmes. JBiol Chan 267 6488-6494,1992. 

Turkey erythrocytes also possess a purinergic receptor, which is linked through a G-protein to a phosphoinositide phospholipase C (Ruiz-Larrea Berrie, 1993). Purinergic receptors are activated by extracellular ATP, ADP and AMP, which occur in low concentration outside cells and have physiological effects. They are known to be released by exocy tosis from adrenal chromaffin granules. 

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

Transduction mechanism Inhibition of adenylyl cyclase stimulation of tyrosine phosphatase activity stimulation of MAP kinase activity activation of ERK inhibition of Ca2+ channel activation stimulation of Na+/H+ exchanger stimulation of AM PA/kainate glutamate channels Inhibition of forskol in-stimulated adenylyl cyclase activation of phos-phoinositide metabolism stimulation of tyrosine phosphatase activity inhibition of Ca2+ channel activation activation of K+ channel inhibition of AM PA/ kainate glutamate channels inhibition of MAP kinase activity inhibition of ERK stimulation of SHP-1 and SHP-2 Inhibition of adenylyl cyclase stimulation of phosphoinositide metabolism stimulation of tyrosine phosphatase activation of K+ channel inhibi-tion/stimulation of MAP kinase activity induction of p53 and Bax Inhibition of adenylyl cyclase stimulation of MAP kinase stimulation of p38 activation of tyrosine phosphatase stimulation of K+ channels and phospholipase A2 Inhibition of adenylyl cyclase activation/ inhibition of phosphoinositide metabolism inhibition of Ca2+ influx activation of K+ channels inhibition of MAP kinase stimulation of tyrosine phosphatase... 

Phorbol esters are promoters that interact with cellular receptors and activate protein kinase C. Usually protein kinase C is activated by Ca++ and diacylglycerol, both of which result from the hydrolysis of phosphoinositides catalyzed by phospholipase C. Phospholipase C is normally activated by several different growth factors. Thus phorbol esters bypass a tightly regulated step in the control of cell growth. Since protein kinase C phosphorylates various proteins, it is not known how this activity participates in establishing a cancerous line of cells. 

S. G., McLaughlin, S., Effect of monolayer surface pressure on the activities of phosphoinositide-specific phospholipase C-beta 1, -gamma 1, and -delta 1, Biochemistry 1994, 33, 3032-3037. 

Other enzymes present in myelin include those involved in phosphoinositide metabolism phosphatidylinositol kinase, diphosphoinositide kinase, the corresponding phosphatases and diglyceride kinases. These are of interest because of the high concentration of polyphosphoinositides of myelin and the rapid turnover of their phosphate groups. This area of research has expanded towards characterization of signal transduction system(s), with evidence of G proteins and phospholipases C and D in myelin. 

The characteristics of the four major classes of histamine receptors are summarized. Question marks indicate suggestions from the literature that have not been confirmed. AA, arachidonic acid DAG, diacylglycerol Iko,2+, calcium-activated potassium current IP3, inositol 1,4,5-trisphosphate NHE, sodium-proton exchange, PKC, protein kinase C NO, nitric oxide PTPLC, phosphoinositide-specific phospholipase C TXA2, thromboxane A2. Has brain-penetrating characteristics after systemic administration. 

H linked intracellular messengers. Activated H receptors are known to activate a pertussis-toxin-insensitive G protein, Gq, that stimulates phosphoinositide-specific phospholipase C (PI-PLC), with the subsequent generation of inositol 1,4,5-trisphosphate (IP3) and diacylglyc-erol (DAG). These two mediators are known to elevate intracellular Ca2+ concentrations and to activate PKC,... 

H, receptors also can stimulate the activity of phospholipase A2 (PLA2), with the subsequent release of arachido-nate and its metabolites. In platelets, this response does not require activation of the phosphoinositide cycle and is inhibited by pertussis toxin, suggesting a second, distinct Gj/o-protein-mediated transduction mechanism. In cells transfected with the H, receptor, PLA2 activation is partially inhibited by pertussis toxin, also suggesting at least two transduction systems [30,34],... 

Genebankaccession numbers are for human clones. fPI-PLC = phosphoinositide-specific phospholipase C. 

The family of heterotrimeric G proteins is involved in transmembrane signaling in the nervous system, with certain exceptions. The exceptions are instances of synaptic transmission mediated via receptors that contain intrinsic enzymatic activity, such as tyrosine kinase or guanylyl cyclase, or via receptors that form ion channels (see Ch. 10). Heterotrimeric G proteins were first identified, named and characterized by Alfred Gilman, Martin Rodbell and others close to 20 years ago. They consist of three distinct subunits, a, (3 and y. These proteins couple the activation of diverse types of plasmalemma receptor to a variety of intracellular processes. In fact, most types of neurotransmitter and peptide hormone receptor, as well as many cytokine and chemokine receptors, fall into a superfamily of structurally related molecules, termed G-protein-coupled receptors. These receptors are named for the role of G proteins in mediating the varied biological effects of the receptors (see Ch. 10). Consequently, numerous effector proteins are influenced by these heterotrimeric G proteins ion channels adenylyl cyclase phosphodiesterase (PDE) phosphoinositide-specific phospholipase C (PI-PLC), which catalyzes the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) and phospholipase A2 (PLA2), which catalyzes the hydrolysis of membrane phospholipids to yield arachidonic acid. In addition, these G proteins have been implicated in... 

Phosphoinositides are cleaved by a family of phosphoinositide-specific phospholipase C isozymes 350... 

In contrast to their more highly expressed counterparts, the 3-phosphoinositides do not serve as substrates for phospholipase C (PLC), the enzyme known to be activated in stimulated phosphoinositide turnover. This observation indicates that the 3-phosphoinositides themselves, rather than their breakdown products, are likely to... 

Katan, M. Families of phosphoinositide-specific phospholipase C structure and function. Biochim. Biophys. Acta 1436 5-17,1998. 

Abnormal G protein functioning dysregulates adenylate cyclase activity, phosphoinositide responses, sodiurrypotassiunVcalcium channel exchange, and activity of phospholipases. Abnormal cyclic adenosine monophosphate and phosphoinositide secondary messenger system activity. 

The Group I mGluRs are coupled to Gaq proteins and stimulation of phospholipase C (PLC). Stimulation of phosphoinositide hydrolysis increases the formation of the... 

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