ライフサイエンスコーパス: PLC-beta

1 PLC beta 2 can be activated by G beta gamma subunits, wh

2 PLC-beta isoforms also function as GTPase-activating pro

3 PLC-beta isozymes are autoinhibited, and several protein

4 PLC-beta signaling is generally thought to be mediated b

5 PLC-beta(3) bound weakly to PA.

6 sphosphate (PIP2) by phospholipase C beta 1 (PLC beta 1) and PLC beta 2 in mixed composition phosphol

7 cid (PA) stimulates phospholipase C-beta(1) (PLC-beta(1)) activity and promotes G protein stimulation

8 (PA) in regulating phospholipase C-beta(1) (PLC-beta(1)) activity was determined.

9 hoinositide-specific phospholipase C beta 2 (PLC-beta 2) is regulated by the alpha q family of G prot

10 ch the PH domain of phospholipase C-beta(2) (PLC-beta(2)), which is regulated by Gbetagamma, replaces

11 Phospholipase C-beta 3 (PLC beta 3) is an important effector enzyme in G protein

12 to PLC-beta(1), the phospholipase C-beta(3) (PLC-beta(3)) isoform was less sensitive to PA, requiring

13 a gamma subunits of both G proteins activate PLC-beta 3, thereby stimulating Ins(1,4,5)P3-dependent C

14 otide-binding proteins (G proteins) activate PLC-betas and in turn are deactivated by these downstrea

15 PAF activated PLC beta 3 through its G alpha(q) protein-coupled recept

16 specifically inhibits G beta gamma-activated PLC-beta 2 activity but not that of the G alpha-activate

17 mble and functionally reconstitute an active PLC-beta(2).

18 beta 1 and PLC beta 2 by 4-6-fold, although PLC beta 1 was more active than PLC beta 2, even at high

19 Although PLC-beta deactivation may contribute to the transient na

20 WNK1 further amplifies PLC-beta signaling when it is phosphorylated by Akt kina

21 which PIP2 was hydrolyzed by PLC beta 1 and PLC beta 2 by 4-6-fold, although PLC beta 1 was more act

22 ) by phospholipase C beta 1 (PLC beta 1) and PLC beta 2 in mixed composition phospholipid monolayers.

23 irect physical interaction of PLC beta 3 and PLC beta 1 isoforms with CaM is supported by pull-down o

24 Physical interaction between CaM and PLC beta 3 is supported by a positive secondary screen i

25 us, PLC beta 1 activity increased 7-fold and PLC beta 2 activity increased 4-fold when the mol % of P

26 ompetitive binding of RACK1, PI3K gamma, and PLC beta to G betagamma.

27 e selectively blocked by G beta antibody and PLC-beta 3 antibody; contractions stimulated by [D-Ala2,

28 tor agonist, were also blocked by G beta and PLC-beta 3 antibodies.

29 show that WNT signaling through Galphao and PLC-beta results in sustained Ca(2+) release via IP(3) a

30 direct interactions between Rac GTPases and PLC-beta isozymes and define a novel role for the PH dom

31 the concentration of Galphaq(GTPgammaS) and PLC-beta activation on lipid bilayers.

32 possess a full complement of G proteins and PLC-beta isozymes were used to identify the PLC-beta iso

33 e affinity between the laterally associating PLC-beta 2 and G beta gamma on membrane surfaces by fluo

34 f the GRK2 RH domain to Galpha(q) attenuates PLC-beta activity.

35 region exerts an inhibitory effect on basal PLC-beta(2) activity.

36 When the linker region was removed, basal PLC-beta(2) enzymatic activity was increased further, su

37 Because PLC beta(3) activation in CHO cells has been shown to be

38 d adenylyl cyclase and phospholipase C beta (PLC beta) activation was measured in each of these cell

39 nvolves stimulation of phospholipase C beta (PLC beta) that results in increased intracellular Ca2+ a

40 Ligand binding, phospholipase C-beta (PLC-beta) activation, inositol 1,4,5-trisphosphate (IP(3

41 bit agonist-stimulated phospholipase C-beta (PLC-beta) activity and inositol 1,4,5-trisphosphate-depe

42 Activation of phospholipase C-beta (PLC-beta) by G protein-coupled receptors typically resul

43 Members of the phospholipase C-beta (PLC-beta) family of proteins are activated either by G a

44 Phospholipase C-beta (PLC-beta) has been implicated to control myriad signalin

45 at G-protein-activated phospholipase C-beta (PLC-beta) interacts with cell polarity proteins Par3 and

46 n-coupled receptors to phospholipase C-beta (PLC-beta) is regulated by coordinate interactions among

47 Phospholipase C-beta (PLC-beta) isoenzymes are key effectors in G protein-coup

48 Mammalian phospholipase C-beta (PLC-beta) isoforms are stimulated by heterotrimeric G pr

49 me Rho family GTPases, phospholipase C-beta (PLC-beta) isoforms hydrolyze phosphatidylinositol 4,5-bi

50 ion of an unidentified phospholipase C-beta (PLC-beta) isozyme and inhibition of adenylyl cyclase.

51 Phospholipase C-beta (PLC-beta) isozymes hydrolyze the membrane lipid phosphat

52 an m2 antagonist, the phospholipase C-beta (PLC-beta) response to CCK-8 and SP, but not CPA, was dec

53 exhibits a more potent phospholipase C-beta (PLC-beta) signal than does wild-type US28, indicating th

54 n of Ca2+ channels and phospholipase C-beta (PLC-beta), the enzyme responsible for generation of the

55 he essential effector, phospholipase C-beta (PLC-beta), which is also known as NORPA.

56 enzymatic activity of phospholipase C-beta (PLC-beta).

57 ian inositol-specific phospholipase C-beta2 (PLC beta 2) and PLC delta 1 differ in their cellular act

58 idylinositol-specific phospholipase C-betas (PLC-betas) are the only PLC isoforms that are regulated

59 consistent with a direct interaction between PLC beta isoforms and CaM.

60 The interactions between PLC-beta and Par proteins are direct and require the ext

61 ral studies showed how Galphaq and Rac1 bind PLC-beta, there is a lack of consensus regarding the Gbe

62 ced the rate at which PIP2 was hydrolyzed by PLC beta 1 and PLC beta 2 by 4-6-fold, although PLC beta

63 coupling to open TRPC3 channels mediated by PLC-beta.

64 ional in cellular assays of phospholipase C (PLC) beta 2 activation and inhibition of G alpha(q)-stim

65 sion of G protein-regulated phospholipase C (PLC) beta 4 in the retina, lateral geniculate nucleus, a

66 nase gamma (PI3K gamma) and phospholipase C (PLC) beta activity, due to the competitive binding of RA

67 sting synergy in activating phospholipase C (PLC) beta.

68 r classes of effectors, the phospholipase C (PLC)-beta isozymes and Rho guanine nucleotide exchange f

69 The phospholipase C (PLC)-beta isozymes differ from the PLC-gamma and PLC-del

70 pid hydrolysis catalyzed by phospholipase C (PLC)-beta isozymes.

71 esicles and incubation with phospholipase C (PLC)-beta resulted in stimulation of PLC-beta activity;

72 xchange chromatography, and phospholipase C (PLC)-beta(1) expression was determined by immunoblot ana

73 ating proteins (GAPs), both phospholipase C (PLC)-betas and RGS proteins, when assayed in solution un

74 ion pathway that includes a phospholipase C (PLC)beta and one cation channel, TRPM5.

75 lation negatively modulates phospholipase C (PLC)beta, enzymes intimately associated with phosphoinos

76 G-protein-activated phospholipase C (PLC-beta) catalyzes the hydrolysis of phosphatidylinosit

77 tion of G-protein-activated phospholipase C (PLC-beta), which suggests direct coupling of the KiSS1 p

78 embers of the G protein-phospholipase Cbeta (PLC-beta) signaling cascade which may allow for rapid de

79 europeptide signaling prompted us to compare PLC-beta isoform expression and activity in four indepen

80 The PH delta PLC beta chimera showed PI(4,5)P2-dependent membrane bin

81 de (PtdIns) specific and G-protein dependent PLC-beta, which stimulates the formation of inositol tri

82 ylation of PLC-gamma and G protein-dependent PLC-beta activation pathways have been reported.

83 mediated signaling mechanism that determines PLC-beta(1) activation.

84 und repair via spatial targeting of distinct PLC-betas within the cell.

85 oes not alter the regulation of the effector PLC-beta(2) by Gbetagamma.

86 dy-state GTP hydrolysis or that GAPs, either PLC-beta or RGS proteins, can substitute for Gbeta gamma

87 We expressed cDNA constructs encoding PLC-beta(2) fragments of different lengths in COS-7 cell

88 ce into enriched lateral domains which favor PLC beta activity.

89 nities of the native enzyme were as follows: PLC-beta 2 >> PLC-delta 1 > PLC-beta 1.

90 ma subunits have a subnanomolar affinity for PLC-beta.

91 esults argue against a recruitment model for PLC-beta activation by G proteins, negatively charged li

92 ysis with polyclonal antibodies specific for PLC-beta(1).

93 iganded form, but increases its affinity for PLC-betas at least 40-200-fold depending on the PLC-beta

94 ergism is unique to PLC-beta3 among the four PLC-beta isoforms and, in general, why one enzyme may re

95 found that PLC beta3 is the major functional PLC beta isoform in murine macrophages.

96 uorescence that G alpha i1(GDP).G beta gamma.PLC-beta 2 can form.

97 t bind Gbetagamma in a FRET-based Gbetagamma-PLC-beta binding assay.

98 e of this response, the mechanisms governing PLC-beta deactivation are poorly characterized.

99 n involves a D1-like dopamine receptor, a Gq/PLC-beta signaling pathway, and calcium release within t

100 were as follows: PLC-beta 2 >> PLC-delta 1 > PLC-beta 1.

101 3 > PLC-beta 1 > PLC-gamma 1 > PLC-delta 1 > PLC-beta 4.

102 atelets decreased in the order PLC-gamma 2 > PLC-beta 2 > PLC-beta 3 > PLC-beta 1 > PLC-gamma 1 > PLC

103 ased in the order PLC-gamma 2 > PLC-beta 2 > PLC-beta 3 > PLC-beta 1 > PLC-gamma 1 > PLC-delta 1 > PL

104 rder PLC-gamma 2 > PLC-beta 2 > PLC-beta 3 > PLC-beta 1 > PLC-gamma 1 > PLC-delta 1 > PLC-beta 4.

105 aling response as evidenced by a decrease in PLC-beta activation and IP3R-mediated calcium store rele

106 fore, intrinsic movement of the PH domain in PLC-beta modulates Gbetagamma access to its binding site

107 he linker region is an inhibitory element in PLC-beta(2) and that Gbetagamma and Galpha(q) do not sti

108 Blocking PH domain motion in PLC-beta by cross-linking it to the EF hand domain inhib

109 catalytic core of PLC-epsilon not present in PLC-beta, gamma, delta, or zeta.

110 existence of a distinct PA binding region in PLC-beta(1).

111 sus regarding the Gbetagamma binding site in PLC-beta.

112 olysis, which is accompanied by an increased PLC-beta mRNA and decreased PLC-alpha mRNA that may repr

113 cerebral cortex and, in contrast, increased PLC-beta mRNA in the frontal cortex and superficial cort

114 Gq GAP activity is characteristic of intact PLC-betas.

115 acial enzyme concentration using 35S-labeled PLC beta 1 confirmed that less enzyme was associated wit

116 d Gbetagamma and the Alexa Fluor 594-labeled PLC-beta pleckstrin homology (PH) domain, we demonstrate

117 uttle box demonstrated that the mice lacking PLC beta 4 were impaired in their visual processing abil

118 A mouse line that lacks PLC beta 4 was generated and the physiological significa

119 Evidence supportive of limited PLC-beta monomer-homodimer equilibrium appears at < or =

120 Cross-linked PLC-beta does not bind Gbetagamma in a FRET-based Gbetag

121 mma) subunits play a role in opioid-mediated PLC beta activation and adenylyl cyclase superactivation

122 A mutant PLC-beta(1) with multiple alanine/glycine replacements f

123 interaction of PA with wild-type and mutant PLC-beta(1) proteins and with fragments of the Galpha(q)

124 and size-exclusion chromatography of native PLC-beta, we observed homodimerization of PLC-beta3 and

125 n with the plasma membrane and activation of PLC beta 1 through direct interaction with, and transact

126 Activation of PLC beta 3 by G alpha and G beta gamma subunits has been

127 ter allergen exposure promoted activation of PLC beta(3), PKC delta, and MARCKS protein desorption fr

128 two domains inhibited the basal activity of PLC beta 2, PLC delta 1, and a G beta gamma-activable PH

129 ese data show that the catalytic activity of PLC beta involves some element of penetration of lipid i

130 arent deficit, suggesting that the effect of PLC beta 4 deficiency on the rod signaling pathway occur

131 tration of tubulin reduced the inhibition of PLC beta 1 observed at high tubulin concentration.

132 Direct physical interaction of PLC beta 3 and PLC beta 1 isoforms with CaM is supported

133 a physiologic role for CaM in modulation of PLC beta activity.

134 membrane-associated tubulin at the offset of PLC beta 1 signaling.

135 delta 1 into remaining C-terminal regions of PLC beta 2.

136 erated and the physiological significance of PLC beta 4 in murine visual function was investigated.

137 The significance of PLC beta signaling in vivo was examined using the apoE-d

138 rain cDNA library with the amino terminus of PLC beta 3 has yielded potential PLC beta 3 interacting

139 a CaM binding site in the amino terminus of PLC beta 3.

140 approximately 123 s) and that activation of PLC-beta 2 by G beta gamma would be sustained without a

141 es of betagamma dimers for the activation of PLC-beta determined with this method were lower than tho

142 membranes are integral for the activation of PLC-beta isozymes by diverse modulators, and we propose

143 s on the gamma subunits in the activation of PLC-beta.

144 alphaq GTPase-activating protein activity of PLC-beta.

145 dney cells without affecting the activity of PLC-beta.

146 tained approximately one-third the amount of PLC-beta 2, whereas PLC-beta 4 was increased threefold.

147 cells (CCh, 58% vs. 421%), and the amount of PLC-beta(1) expressed in g-HCM cells, compared with that

148 proved and sensitive method for the assay of PLC-beta activity.

149 The binding of PLC-beta(1) to PA containing phospholipid vesicles was a

150 osphatidic acid also enhanced the binding of PLC-beta(1) to SLUV but was less effective in stimulatin

151 PA promoted the binding of PLC-beta(1) to sucrose-loaded unilamellar vesicles (SLUV

152 thermore, we have shown that coexpression of PLC-beta with Par proteins induces transcriptional activ

153 agonists is attributable to a deficiency of PLC-beta 2.

154 Thus, the PH domain of PLC-beta 1 interacts with G-beta gamma in isolation, but

155 Most of the COOH-terminal domain of PLC-beta isozymes is predicted to be helical, and three

156 We found that attachment of the PH domain of PLC-beta(2) onto PLC-delta(1) not only causes the membra

157 The pleckstrin homology domain of PLC-beta(2) was required for its targeting to the membra

158 the affinities of the isolated PH domains of PLC-beta 1 and -beta 2 (PH-beta 1 and PH-beta 2, respect

159 de evidence consistent with the existence of PLC-beta homodimers in a whole-cell context, using fluor

160 hosphate production as well as expression of PLC-beta(1) are altered in g-HCM cells compared with tha

161 There are four well-characterized forms of PLC-beta and all of them are activated to various extent

162 The fraction of PLC-beta cross-linked is proportional to the fractional

163 A 100 kDa catalytic fragment of PLC-beta(1) lacking amino acid residues C-terminal to Hi

164 on by G beta gamma, a series of fragments of PLC-beta 3 as glutathione-S-transferase (GST) fusion pro

165 C2 domain (GTP-bound alpha subunit of Gq) of PLC-beta; the PH domain [PtdIns(3,4,5)P3] and Src homolo

166 ately expressed amino and carboxyl halves of PLC-beta(2) could associate to form catalytically active

167 The importance of PLC-beta in neuropeptide signaling prompted us to compar

168 In contrast, inhibitors of PLC-beta, hexadecylphosphocholine and, had no effect on

169 re, our data suggest that the interaction of PLC-beta with cell polarity Par proteins may serve as a

170 rior research suggests that some isoforms of PLC-beta may exist and function as dimers.

171 Membrane localization of PLC-beta isozymes is therefore likely mediated by both t

172 has been widely used for the measurement of PLC-beta activity in vitro.

173 treme C-terminal-specific sequence motifs of PLC-beta and the PDZ (PSD95/Dlg/ZO-1) domains of Par pro

174 Phosphorylation of PLC-beta leads to the inhibition of G-protein-activated

175 an N-terminal G beta gamma binding region of PLC-beta 3 that is involved in activation of the enzyme.

176 To define specific regions of PLC-beta 3 that are involved in binding and activation b

177 The isoform dependence for PA regulation of PLC-beta activity as well as the role of PA in modulatin

178 s the role of PA in modulating regulation of PLC-beta activity by protein kinase C (PKC) and G protei

179 WNK1 activity is essential for regulation of PLC-beta signaling by G(q)-coupled receptors, and basal

180 athway for conferring specific regulation of PLC-beta(1) in response to increases in cellular PA leve

181 PA regulation of PLC-beta(1) requires unique residues that are not requir

182 PA may have a key role in the regulation of PLC-beta(1) signaling in cells.

183 consistent with a model for PA regulation of PLC-beta(1) that involves cooperative interactions, prob

184 ments and the mechanism for PA regulation of PLC-beta(1).

185 To further understand the regulation of PLC-beta(2) by G proteins and the functional roles of PL

186 WNK1 is a novel regulator of PLC-beta that acts by controlling substrate availability

187 on of G alpha i1(GDP) results in reversal of PLC-beta 2 activation by G beta gamma during the time of

188 2) by G proteins and the functional roles of PLC-beta(2) structural domains, we tested whether the se

189 e results demonstrate that PA stimulation of PLC-beta activity is tightly regulated, suggesting the e

190 pase C (PLC)-beta resulted in stimulation of PLC-beta activity; however, when this activation precede

191 Stimulation of PLC-beta by WNK1 and by Galpha(q) are synergistic; WNK1

192 PA increased the stimulation of PLC-beta(1) activity by G alpha q but had little effect

193 increased receptor-G protein stimulation of PLC-beta(1) activity in membranes.

194 PKC, however, inhibited PA stimulation of PLC-beta(1) activity through a mechanism dependent on th

195 tivity and promotes G protein stimulation of PLC-beta(1) activity.

196 PA also modulates Galpha(q) stimulation of PLC-beta(1).

197 PKC had little effect on PA stimulation of PLC-beta(3) activity.

198 not solvent-exposed in crystal structures of PLC-beta, necessitating conformational rearrangement to

199 protein kinase C (PKC) in the termination of PLC-beta activation induced by endogenous P2Y(2) puriner

200 f PLC-delta(1) to become similar to those of PLC-beta(2), but also results in a Gbetagamma-regulated

201 the cyclooxygenases, and underexpression of PLC-beta(1).

202 nism of action in which the COOH terminus of PLC-betas can interact with Gq and with other PLC-beta1

203 t of potential effects on the receptor or on PLC-beta.

204 r-mediated activation of either PLC-gamma or PLC-beta.

205 t with antibodies to PLC-beta3 but not other PLC-beta isozymes, and by antibodies to Gbeta but not Ga

206 Relative to other PLC-beta isoenzymes, PLC-betaX was less sensitive to sti

207 ta gamma activation of the PH-PLC delta 1 PH-PLC beta 2 enzymes in a concentration-dependent manner,

208 terminus of PLC beta 3 has yielded potential PLC beta 3 interacting proteins including calmodulin (Ca

209 nt responses mediated by the same G protein, PLC-beta activity was measured in cells stimulated seque

210 he enzymatic profiles of previously purified PLC-beta isozymes, the purified fragment of PLC-epsilon

211 capacity to directly engage various purified PLC-beta isozymes.

212 activities previously observed with purified PLC-beta or PLC-epsilon isozymes.

213 is primarily via signalling through the G(q)/PLC-beta pathway and subsequent activation of Ca(2+)-dep

214 protein interactions that may also regulate PLC beta 3 function.

215 lates basal and receptor-G protein-regulated PLC-beta(1) activity.

216 d the interaction energies between the RGS4, PLC-beta, G-betagamma, and both deactivated (GDP-bound)

217 However, the biological effects of selective PLC-beta isozymes are poorly understood.

218 In the current study, we used selective PLC-beta and G protein antibodies to identify the PLC-be

219 of Rac (Rac1, Rac2, and Rac3) both stimulate PLC-beta activity in vivo and bind PLC-beta2 and PLC-bet

220 at Gbetagamma and Galpha(q) do not stimulate PLC-beta(2) through easing the inhibition of enzymatic a

221 tion and inhibition of G alpha(q)-stimulated PLC beta 1 activity.

222 gment also inhibited G beta gamma-stimulated PLC-beta activity in a reconstitution system, while havi

223 o significant effect on G alpha q-stimulated PLC-beta 3 activity.

224 naling phospholipid, binds to and stimulates PLC-beta(1) through a mechanism that requires the PLC-be

225 ing of Par proteins with PLC-beta stimulates PLC-beta enzymatic activity, leading to the hydrolysis o

226 lar biosensors, we show that WNK1 stimulates PLC-beta signaling in cells by promoting the synthesis o

227 is more potent and effective in stimulating PLC-beta activity than the beta1gamma1 dimer.

228 recipitation assays of differentially tagged PLC-beta constructs and size-exclusion chromatography of

229 and transcribed amino- and carboxyl-terminal PLC beta 3 revealed CaM binding at a putative amino-term

230 ld, although PLC beta 1 was more active than PLC beta 2, even at high surface pressure.

231 ucleus, and superior colliculus implies that PLC beta 4 may play a role in the mammalian visual proce

232 d electroretinographic results indicate that PLC beta 4 plays a significant role in mammalian visual

233 Our data suggest that PLC-beta is an important mediator of both SCLC and NSCLC

234 In addition, the PLC beta 4-null mice showed 4-fold reduction in the maxi

235 veal any significant differences between the PLC beta 4-null and wild-type littermates, nor were ther

236 the cells with ACh and an m3 antagonist, the PLC-beta response to CPA, but not CCK-8 or SP, was decre

237 eased, whereas after treatment with CPA, the PLC-beta response mediated by G(i3) only was decreased.

238 eta and G protein antibodies to identify the PLC-beta isozyme activated by opioid receptors in intest

239 PLC-beta isozymes were used to identify the PLC-beta isozyme and the G proteins coupled to it and to

240 concentration dependence was observed in the PLC-beta(1) mutant.

241 rectly phosphorylates serine residues of the PLC-beta 2 protein both in vivo and in vitro.

242 nesis, we identify a hydrophobic face of the PLC-beta PH domain as the Gbetagamma binding interface.

243 eolin-3 and prevented desensitization of the PLC-beta response mediated only by other G(q/11)-coupled

244 We find that a large portion of the PLC-beta-Galphaq association energy lies within the 400

245 -betas at least 40-200-fold depending on the PLC-beta isoform.

246 eta(1) through a mechanism that requires the PLC-beta(1) C-terminal domain.

247 larly, after treatment with CCK-8 or SP, the PLC-beta response mediated by G(q/11) only was decreased

248 The off rate shows that the PLC-beta 2.G beta gamma complexes are long-lived ( appro

249 e that G alpha(GDP) subunits can bind to the PLC-beta 2.G beta gamma complex to allow for rapid deact

250 C (PLC-betaX) that exhibits homology to the PLC-beta class of isoenzymes.

251 mooth muscle and the G proteins to which the PLC-beta isozyme and adenylyl cyclase are coupled.

252 Gq, the G protein class that stimulates the PLC-betas in response to receptors.

253 Gbetagamma and Galpha(q) activated these PLC-beta(2) constructs equally in the presence or absenc

254 This PLC-beta 3 fragment also inhibited G beta gamma-stimulat

255 Gbetagamma subunits interact with all three PLC-beta isotypes, but only showed strong binding to PLC

256 ng to PLC-beta2, and activation of the three PLC-betas by Gbetagamma subunits parallels this behavior

257 cascades and suggest that signaling through PLC-beta and PKC plays a central role in MCMV pathogenes

258 Thus, PLC beta 1 activity increased 7-fold and PLC beta 2 acti

259 As compared to PLC-beta(1), the phospholipase C-beta(3) (PLC-beta(3)) i

260 revealed efficient activation in response to PLC-beta or PLC-gamma activation, which was independent

261 inhibitor of constitutive US28 signaling to PLC-beta, we demonstrate that CX3CL1 functions as an ago

262 The reconstituted enzymes, like wild-type PLC-beta(2), were activated by Gbetagamma; when the C-te

263 as active or more active than the wild-type PLC-beta(2).

264 We propose that unliganded PLC-beta exists in equilibrium between a closed conforma

265 ation preceded reconstitution into vesicles, PLC-beta activity was markedly diminished.

266 rom G(q) is necessary for WNK1 signaling via PLC-beta.

267 one-third the amount of PLC-beta 2, whereas PLC-beta 4 was increased threefold.

268 elative PLC stimulation by PA increased with PLC-beta(1) concentration in a manner suggesting coopera

269 Binding of Par proteins with PLC-beta stimulates PLC-beta enzymatic activity, leading

270 cribing membrane-mediated allosterism within PLC-beta isozymes.

271 a(q) reveals a conserved module found within PLC-betas and other effectors optimized for rapid engage