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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

100 3 > PLC-beta 1 > PLC-gamma 1 > PLC-delta 1 > PLC-beta 4.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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