ライフサイエンスコーパス: PDE6

1 te may be regulation of phosphodiesterase 6 (PDE6).

2 ily of cyclic nucleotide phosphodiesterases (PDE6).

3 r G-protein effector cGMP phosphodiesterase (PDE6).

4 on of cyclic nucleotide phosphodiesterase 6 (PDE6).

5 visual effector enzyme phosphodiesterase-6 (PDE6).

6 s due to defective cGMP phosphodiesterase-6 (PDE6).

7 distinct mechanisms of Pgamma inhibition of PDE6.

8 5 inhibitors to probe the catalytic sites of PDE6.

9 rim marker peripherin-2 and endogenous frog PDE6.

10 ion between the GAF and catalytic domains in PDE6.

11 the cGMP-bound GAF A domain of chicken cone PDE6.

12 own about direct allosteric communication of PDE6.

13 ificity of the interaction between GARP2 and PDE6.

14 ors was determined for purified rod and cone PDE6.

15 evated cGMP levels, but none fully inhibited PDE6.

16 ot require Gtalpha interaction with RGS9 and PDE6.

17 ibitors were equally effective in inhibiting PDE6.

18 ance of the unique heterodimerization of rod PDE6.

19 afil with better selectivity toward PDE1 and PDE6.

20 cGMP to the regulatory GAFa-GAFb domains of PDE6.

21 cones indicating functional substitution of PDE6.

22 tic activity of heterologously expressed rod PDE6.

23 a dynamic equilibrium between transducin and PDE6.

24 binding affinity to levels characteristic of PDE6.

25 presence of the inhibitory Pgamma-subunit of PDE6.

26 that the multimeric rod phosphodiesterase 6 (PDE6), a prenylated protein and RCE1 substrate, was unab

27 lation of cGMP binding to the GAF domains of PDE6, a photoexcitable peptide probe corresponding to th

28 to defects in rod-specific phosphodiesterase PDE6, a tetramer consisting of catalytic (PDE6alpha and

29 class-specific differences between PDE5 and PDE6 account for the biochemical and pharmacological dif

30 sphorylation sites can influence the rate of PDE6 activation and deactivation and raise the possibili

31 gly, we hypothesize that the initial step in PDE6 activation involves an interaction of transducin-al

32 ew insights into the molecular mechanisms of PDE6 activation.

33 ing increases in proportion to the extent of PDE6 activation.

34 providing insight into the regulation of the PDE6 activation/deactivation cycle.

35 Although major steps in the PDE6 activation/deactivation pathway have been identifie

36 causes CSNB through incomplete inhibition of PDE6 activity by Pgamma, which leads to desensitization

37 ic manner, with only one-half of the maximum PDE6 activity efficiently attained during visual excitat

38 TPR domain of AIPL1 also failed to modulate PDE6 activity efficiently.

39 f GARP2 for PDE6 and its ability to regulate PDE6 activity in its dark-adapted state suggest a novel

40 for a nonsense Pde6b(rd1) allele, absence of PDE6 activity is associated with retinal disease similar

41 exhibit a hypomorphic phenotype with partial PDE6 activity that may result in an increased Ca(2+) to

42 Before degeneration, PDE6beta expression and PDE6 activity were reduced.

43 lts show that the PDE6gamma binding sites of PDE6 alpha and beta are accessible to excess (presumably

44 rod PDE6 (alphabeta) and the absence of cone PDE6 (alpha') catalytic subunits.

45 alphabeta), while the catalytic core of cone PDE6 (alpha') is a homodimer.

46 aches, we demonstrated the expression of rod PDE6 (alphabeta) and the absence of cone PDE6 (alpha') c

47 role as a chaperone of phosphodiesterase 6 (PDE6), an effector enzyme of the visual transduction cas

48 lacked interaction with the gamma-subunit of PDE6, an effector protein in phototransduction.

49 Reconstitution of PDE6 and activated G(alphat), on the surface of large un

50 Progress in research on PDE6 and AIPL1 has been severely hampered by failure to

51 e effectiveness of PDE inhibitors to inhibit PDE6 and disrupt the cGMP signaling pathway during visua

52 wed a high degree of homology with mammalian PDE6 and equally distant relationships with the rod and

53 a-GDP, the PDE6gamma may dissociate from the PDE6 and exchange with a cytoplasmic pool.

54 Lack of interaction disrupts trafficking of PDE6 and GRK1 to their destination, the photoreceptor ou

55 eracts with the catalytic subunit (alpha) of PDE6 and is needed for the proper assembly of functional

56 The high binding affinity of GARP2 for PDE6 and its ability to regulate PDE6 activity in its da

57 s of PDE inhibitors on purified rod and cone PDE6 and on intact rod outer segments (ROS) were charact

58 f recombinant frog PrBP/delta can solubilize PDE6 and prevent its activation by transducin.

59 sential for the intracellular trafficking of PDE6 and survival of photoreceptor cells.

60 rated that AIPL1 is an obligate chaperone of PDE6 and that it enables low yield functional folding of

61 ons with the catalytic alphabeta-subunits of PDE6 and the alpha-subunit of transducin (alpha(t)).

62 utations in AIPL1 are thought to destabilize PDE6 and thereby cause Leber congenital amaurosis type 4

63 alpha(t)GTPgammaS co-immunoprecipitated with PDE6 and vice versa in a Pgamma-dependent manner.

64 robust decrease in rod phosphodiesterase 6 (PDE6) and G-protein receptor kinase-1 (GRK1) levels.

65 nts, but their effects on photoreceptor PDE (PDE6) and photoreceptor cells are poorly understood.

66 y the opposing actions of phosphodiesterase (PDE6) and retinal guanylyl cyclases (GCs), and mutations

67 A map revealed previously unseen features of PDE6, and each domain was readily fit with high resoluti

68 Transducin activation of PDE6 appears to require interaction with both the C term

69 he idea that multiple structural elements of PDE6 are highly susceptible to misfolding during heterol

70 spontaneously activated and light-activated PDE6 are modulated.

71 hen the regulatory GAF domains of bovine rod PDE6 are occupied by cGMP.

72 e show that the catalytic subunit (alpha) of PDE6 associates with AIPL1 in retinal extracts.

73 the effector enzyme cGMP phosphodiesterase (PDE6) at the surface of disk membranes.

74 gy model of the GAF-A domain of chicken cone PDE6 based on the crystal structure of mouse PDE2A GAF-B

75 ide-containing vesicles revealed patterns of PDE6 binding and PDE6-enhanced G(alphat)-GTPgammaS bindi

76 e demonstrated that GARP2 is a high affinity PDE6-binding protein and that PDE6 co-purifies with GARP

77 ndant in retinal cells, selectively released PDE6 (but not GARP2) from rod outer segment membranes, d

78 protein-stimulated activation of endogenous PDE6, but not trypsin-stimulated PDE activity.

79 no acids decreased the Michaelis constant of PDE6 by 2.5-fold.

80 as been hypothesized to reduce activation of PDE6 by transducin, thereby desensitizing the photorespo

81 ivation of the cyclic GMP phosphodiesterase (PDE6) by transducin is the central event of visual signa

82 n (PrBP/delta) indicated the location of the PDE6 C-terminal prenylations.

83 We conclude that either rod or cone PDE6 can effectively couple to the cone phototransductio

84 titutive activation of the phosphodiesterase PDE6 cascade in darkness.

85 Transducin activation of PDE6 catalysis critically depends on the presence of Ile

86 subunit (Pgamma), known to directly inhibit PDE6 catalysis, was increased approximately 2-fold by li

87 The activity of rod PDE6 catalytic alpha- and beta-subunits is blocked in th

88 PDEs that form catalytic homodimers, the rod PDE6 catalytic core is a heterodimer composed of alpha a

89 Rod PDE6 catalytic core is composed of two distinct subunits

90 identical PDE6alpha' subunits form the cone PDE6 catalytic core.

91 integrative structural determination of the PDE6 catalytic dimer (alphabeta), based primarily on che

92 In solution, the PDE6 catalytic dimer (Palphabeta) exhibits a more asymme

93 to bind to either the PDE6 holoenzyme or the PDE6 catalytic dimer reconstituted with Pgamma, consiste

94 PDE6 fail to exceed 50% of the value for the PDE6 catalytic dimer.

95 antly alter catalysis of the fully activated PDE6 catalytic dimer.

96 ange was detected upon ligand binding to the PDE6 catalytic dimer.

97 Here, crystal structures of a chimaeric PDE5/PDE6 catalytic domain (PDE5/6cd) complexed with sildenaf

98 s-of-function mutagenesis of a chimeric PDE5/PDE6 catalytic domain and gain-of-function mutagenesis o

99 The PDE6 catalytic subunit contains a catalytic domain and r

100 It is not known whether this difference in PDE6 catalytic subunit identity contributes to the funct

101 A single PDE6 catalytic subunit transcript was found in the sea l

102 ariations between PDE6 subunits preclude rod PDE6 catalytic subunits from coupling to the cone photot

103 ng implies that the retention of the -AAX in PDE6 catalytic subunits in Rce1(-/-) mice is responsible

104 The activity of PDE6 catalytic subunits is controlled by the Pgamma-subu

105 d rhodopsin kinase (GRK1) and prenylated rod PDE6 catalytic subunits partially mislocalized in Pde6d(

106 When PDE6 catalytic subunits were reconstituted with portions

107 in cGMP metabolism in rods, most notably the PDE6 catalytic subunits, and severely reduced sensitivit

108 e binding is a consequence of prenylation of PDE6 catalytic subunits, whereas soluble PDE6 is purifie

109 affinity and selectivity of dimerization of PDE6 catalytic subunits.

110 aG38D function, its poor ability to activate PDE6 (cGMP phosphodiesterase) and decreased GTPase activ

111 high affinity PDE6-binding protein and that PDE6 co-purifies with GARP2 during several stages of chr

112 ma with Pbeta as compared with Palpha in the PDE6 complex has not been reported.

113 In intact ROS, high PDE6 concentrations, binding of the gamma-subunit to the

114 Holo-PDE6 consists of two similar catalytic subunits (Palphab

115 PDE6 contains two regulatory GAF domains, of which one (

116 light produces a Ca(2+)-mediated decrease in PDE6 decay rate, with the novel feature that both sponta

117 Stop), which allows us to temporally correct PDE6-deficiency.

118 Consistent with the selectivity of PDE6 dimerization in vivo, efficient heterodimerization

119 a (PDE6 gamma) inhibitory subunit of the rod PDE6 effector enzyme plays a central role in the turning

120 * and activation of the phosphodiesterase 6 (PDE6) effector molecule occurs with less gain.

121 sicles revealed patterns of PDE6 binding and PDE6-enhanced G(alphat)-GTPgammaS binding, consistent wi

122 Affected retinas lacked PDE6 enzymatic activity.

123 e PDE6B subunit causes a loss of function in PDE6 enzyme and in adult mice homozygous to the mutation

124 The rod PDE6 enzyme expressed in cone cells is active and contri

125 cone photoreceptor neurons utilize discrete PDE6 enzymes that are crucial for phototransduction.

126 hibited trypsin-activated lamprey and bovine PDE6 enzymes.

127 Several classes of PDE inhibitors inhibit PDE6 equally as well as the PDE family to which they are

128 In addition, rod PDE6 expressed in cone cells couples to the light signal

129 re compared with rd1/+ rods based on similar PDE6 expression.

130 rafficking of M-cone opsin and restored cone PDE6 expression.

131 hydrolytic activity of transducin-activated PDE6 fail to exceed 50% of the value for the PDE6 cataly

132 etinal rod and cone cGMP phosphodiesterases (PDE6 family) function as the effector enzyme in the vert

133 Retinal rod cGMP phosphodiesterase (PDE6 family) is the effector enzyme in the vertebrate vi

134 To understand the evolution of the PDE6 family, we have examined PDE6 in lamprey, an ancien

135 The binding affinity of PDE6 for pharmacological inhibitors or for the C-termina

136 targeting of prenylated proteins (including PDE6) from their site of synthesis in the inner segment

137 alyzed the consequences of this mutation for PDE6 function using a Pgamma-sensitive PDE6alpha'/PDE5 c

138 e are caused by a loss in phosphodiesterase (PDE6) function.

139 of the high specificity for cGMP binding to PDE6 GAF-A.

140 ha' chimeras by Pgamma supported the role of PDE6 GAFa but not GAFb domains in the interaction with P

141 Furthermore, our analysis indicated that the PDE6 GAFa domains contain major structural determinants

142 Several studies have shown that PDE6 gamma can be phosphorylated at two threonines, T22

143 ents suggest that the polycationic domain of PDE6 gamma containing these two phosphorylation sites ca

144 that phosphorylation or dephosphorylation of PDE6 gamma could modify the time course of transduction,

145 hydrolysis of the second messenger cGMP, and PDE6 gamma in association with RGS9-1 and the other GAP

146 isual transduction cascade, since binding of PDE6 gamma to the transducin alpha subunit (T alpha) ini

147 The phosphodiesterase 6 gamma (PDE6 gamma) inhibitory subunit of the rod PDE6 effector

148 C-B inhibition by the cone- and rod-specific PDE6 gamma-subunits (Pgamma) were comparable.

149 ntly inhibited by the cone- and rod-specific PDE6 gamma-subunits.

150 ts point to a high degree of conservation of PDE6 genes during the vertebrate evolution.

151 ession of the cGMP phosphodiesterase type 6 (PDE6) genes, we have characterized the promoter of the h

152 compound with high specificity for PDE5 over PDE6, had a similar action.

153 understanding the structure and function of PDE6 has been hindered by lack of an expression system o

154 The key dimerization selectivity module of PDE6 has been localized to a small segment within the GA

155 catalytic cGMP binding to the GAF domains of PDE6 has been localized to amino acids 27-30 of Pgamma.

156 esults demonstrate that both subunits of the PDE6 heterodimer are able to bind ligands to the enzyme

157 he alpha- and beta-subunits of the activated PDE6 heterodimer.

158 The functional significance of rod PDE6 heterodimerization and conserved differences betwee

159 edge about the molecular organization of the PDE6 holoenzyme (alphabetagammagamma).

160 e cGMP-dependent regulation mechanism of the PDE6 holoenzyme and its inhibition through Pgamma bindin

161 activity of the nonactivated, membrane-bound PDE6 holoenzyme at concentrations equivalent to its endo

162 Here, we characterize the PDE6 holoenzyme by integrative structural determination

163 [(3)H]vardenafil fails to bind to either the PDE6 holoenzyme or the PDE6 catalytic dimer reconstitute

164 Binding of activated transducin to PDE6 holoenzyme resulted in a concentration-dependent in

165 the cGMP binding properties of chicken cone PDE6 holoenzyme were very similar to those of the bacter

166 PrBP/delta bound to the PDE6 holoenzyme with high affinity (K(D) = 6.2 nm) and i

167 transducin activation of membrane-associated PDE6 holoenzyme, [(3)H]vardenafil binding increases in p

168 ilable on the properties of the chicken cone PDE6 holoenzyme, we also characterized the native PDEs o

169 binds cGMP and regulates the activity of the PDE6 holoenzyme.

170 in quantitatively separating GARP2 from the PDE6 holoenzyme.

171 mmalian rod photoreceptor phosphodiesterase (PDE6) holoenzyme is isolated in both a membrane-associat

172 retinal cyclic GMP (cGMP) phosphodiesterase (PDE6) holoenzyme.

173 re, transducin relieves Pgamma inhibition of PDE6 in a biphasic manner, with only one-half of the max

174 ly hampered by failure to express functional PDE6 in a heterologous expression system.

175 A structure of PDE6 in complex with prenyl-binding protein (PrBP/delta)

176 The structure of holo-PDE6 in complex with the ROS-1 antibody Fab fragment was

177 rBP/delta per PDE6) to serve as a subunit of PDE6 in either mammalian or amphibian photoreceptors.

178 ith retina-specific Rce1 knock-out mice, rod PDE6 in Icmt-deficient mice trafficked normally to the p

179 olution of the PDE6 family, we have examined PDE6 in lamprey, an ancient vertebrate group.

180 In contrast to bovine ROS, all of the PDE6 in purified frog ROS is membrane-associated.

181 a transgenic mouse model that expresses cone PDE6 in rods and show that the cone PDE6 isoform is part

182 Since rod PDE6 in the Rambusch CSNB is a catalytic heterodimer of

183 able to reverse the transducin activation of PDE6 (in contrast to a previous study) nor did it signif

184 examined the role of cGMP phosphodiesterase (PDE6) in this difference by expressing cone PDE6 (PDE6C)

185 prinast (10 microM, an inhibitor of PDE5 and PDE6) induced a slowly developing and sustained depressi

186 ow the determinants and the mechanism of the PDE6 inhibition by Pgamma and suggest the conformational

187 bution of the H-loop-M-loop interface to the PDE6 inhibition by the Pgamma C-terminus.

188 th fewer adverse side effects resulting from PDE6 inhibition.

189 hibitor (K(i) = 0.2 nM), was the most potent PDE6 inhibitor tested (K(i) = 0.7 nM).

190 ost PDE5-selective inhibitors were excellent PDE6 inhibitors.

191 How the PDE6 inhibitory gamma-subunit (Pgamma) interacts with th

192 In contrast, two different PDE6 inhibitory Pgamma subunits, a cone-type Pgamma1 and

193 The retinal phosphodiesterase (PDE6) inhibitory gamma-subunit (PDEgamma) plays a centra

194 ion state, the cyclic GMP phosphodiesterase (PDE6) inhibitory gamma-subunit (PDEgamma) stimulates GTP

195 gion of Pgamma is a primary docking site for PDE6-interacting proteins involved in the activation/ina

196 The cGMP phosphodiesterase (PDE6) involved in visual transduction in photoreceptor c

197 The catalytic core of rod PDE6 is a unique heterodimer of PDE6A and PDE6B catalyti

198 Rod PDE6 is composed of heterodimeric catalytic subunits (al

199 r demonstrate that this rapid degradation of PDE6 is due to the essential role of AIPL1 in the proper

200 PDE6 is membrane associated through isoprenyl membrane a

201 We conclude that allosteric regulation of PDE6 is more complex than for PDE5 and is dependent on i

202 A system for efficient expression of rod PDE6 is not available.

203 ly, yet its significance for the function of PDE6 is poorly understood.

204 ibitory gamma-subunit for the active site of PDE6 is proposed to reduce the effectiveness of drugs at

205 of PDE6 catalytic subunits, whereas soluble PDE6 is purified with a 17-kDa prenyl-binding protein (P

206 Interestingly, we also found that functional PDE6 is required for trafficking of M-opsin to cone oute

207 Retinal cGMP phosphodiesterase (PDE6) is a key enzyme in vertebrate phototransduction.

208 Rod cGMP phosphodiesterase 6 (PDE6) is a key enzyme of the phototransduction cascade,

209 Phosphodiesterase-6 (PDE6) is a multisubunit enzyme that plays a key role in

210 gulation of photoreceptor phosphodiesterase (PDE6) is controlled by both allosteric mechanisms and ex

211 Rod phosphodiesterase (PDE6) is the central effector enzyme in vertebrate visua

212 Photoreceptor phosphodiesterase (PDE6) is the central effector enzyme in visual excitatio

213 Photoreceptor cGMP phosphodiesterase (PDE6) is the central enzyme in the visual transduction c

214 Phosphodiesterase 6 (PDE6) is the effector enzyme in the phototransduction ca

215 Photoreceptor cGMP phosphodiesterase (PDE6) is the effector enzyme in the vertebrate visual tr

216 Phosphodiesterase-6 (PDE6) is the key effector enzyme of the phototransductio

217 Phosphodiesterase-6 (PDE6) is the key effector enzyme of the vertebrate photo

218 of rod photoreceptor cGMP phosphodiesterase (PDE6) is the presence of inhibitory subunits (Pgamma), w

219 Retinal photoreceptor phosphodiesterase (PDE6) is unique among the phosphodiesterase enzyme famil

220 ransduction cascade, cGMP phosphodiesterase (PDE6), is regulated by its gamma-subunit (Pgamma), whose

221 hosphodiesterase of rod photoreceptor cells, PDE6, is the key effector enzyme in phototransduction.

222 ses cone PDE6 in rods and show that the cone PDE6 isoform is partially responsible for the difference

223 to be regulated by the PDE5 rather than the PDE6 isoform.

224 of cGMP but is not strictly conserved among PDE6 isoforms.

225 immunohistochemistry, and assay for retinal PDE6 levels and enzymatic activity.

226 a robust pharmacokinetic profile without any PDE6 liability.

227 onic region of Pgamma to the GAFa domains of PDE6 may lead to a stabilization of the noncatalytic cGM

228 DE6gamma remains attached to the rest of the PDE6 molecule, but after conversion of Talpha-GTP to Tal

229 Zaprinast was the only drug that inhibited PDE6 more potently than did PDE5.

230 indicating that some basic regulation of the PDE6 multisubunit enzyme was maintained albeit by a unkn

231 gs rod survival caused by elevated cGMP in a PDE6 mutant mouse model.

232 Previous work using viral gene therapy on PDE6-mutant mouse models demonstrated photoreceptors can

233 ated cGMP and Ca2+, which are induced by the Pde6 mutation.

234 the mechanisms of visual diseases linked to PDE6 mutations.

235 ed a cone-dominated mouse model lacking cone PDE6 (Nrl(-/-) cpfl1).

236 linked to the highly reduced levels of cone PDE6 observed in the hAIPL1 transgenic mice.

237 metabolic turnover and phosphodiesterase 6 (PDE6) off-target activity limited its advancement.

238 defects in photoreceptor phosphodiesterase (PDE6) or regulation of retinal guanylyl cyclase (retGC).

239 from photoreceptors by the guanylate cyclase/PDE6 pair in phototransduction.

240 one PDE6 (PDE6C) in rd1/rd1 rods lacking rod PDE6 (PDE6AB) using transgenic mice.

241 (PDE6) in this difference by expressing cone PDE6 (PDE6C) in rd1/rd1 rods lacking rod PDE6 (PDE6AB) u

242 Two histone-activated PDE6 peaks were separated by ion exchange chromatography

243 Identification of the determinants for the PDE6-Pgamma interaction offers insights into the evoluti

244 PDE6 (phosphodiesterase-6) is the effector molecule in t

245 The stoichiometry of PDE6-PrBP/delta binding and the mechanism by which the P

246 delta binding and the mechanism by which the PDE6-PrBP/delta complex assembles have not been fully ch

247 ve developed a rapid purification method for PDE6-PrBP/delta from bovine rod outer segments utilizing

248 PDE6 present in the inner segment of Rce1-deficient phot

249 iated with mutations in phosphodiesterase-6 (PDE6) provokes a metabolic aberration in rod cells that

250 ttermates to investigate whether PDE5 and/or PDE6 regulates excitatory synaptic transmission in the h

251 The photoreceptor phosphodiesterase (PDE6) regulates the intracellular levels of the second m

252 een identified, mechanistic understanding of PDE6 regulation is limited by the lack of knowledge abou

253 ion and characterization of the chicken cone PDE6 regulatory GAF-A and GAF-B domains.

254 which AIPL1 and Pgamma are co-expressed with PDE6 represents an effective tool for probing structure-

255 used to quantify [(3)H]vardenafil binding to PDE6 required histone II-AS to stabilize drug binding to

256 t, the half-maximal activation of bovine rod PDE6 required markedly higher concentrations of Galpha(t

257 ) with the corresponding class-specific cone PDE6 residues (P773E, I778V, E780L, F787W, E796V, D803P,

258 Introduction of PDE6 residues into the background of the PDE5 protein se

259 ting vascular smooth muscle contraction) and PDE6 (responsible for regulating visual transduction in

260 his disease, defects in the alpha-subunit of PDE6 result in a progressive loss of photoreceptors and

261 The lamprey PDE6 sequence showed a high degree of homology with mamm

262 Because PDE6 shares structural and pharmacological similarities

263 This analysis revealed the key role of PDE6-specific residues within the catalytic domain M-loo

264 raction with HSP90 and modulate the rod cGMP PDE6 stability and activity.

265 entrifuge, we examined allosteric changes in PDE6 structure and protein-protein interactions with its

266 ther, these results rule out PrBP/delta as a PDE6 subunit and implicate PrBP/delta in the transport a

267 The catalytic PDE6 subunit was present in the photoreceptors of both t

268 ed as a putative rod cGMP phosphodiesterase (PDE6) subunit in the retina, where it is relatively abun

269 Prenylated PDE6 subunits and G-protein coupled receptor kinase 1 (G

270 arly shows that in the absence of AIPL1, rod PDE6 subunits are rapidly degraded by proteasomes.

271 cial link between AIPL1 and the stability of PDE6 subunits is not known.

272 It is not known if variations between PDE6 subunits preclude rod PDE6 catalytic subunits from

273 r utilizes discrete catalytic and inhibitory PDE6 subunits to fulfill its physiological tasks, i.e. t

274 t the affected retinas also lacked the other PDE6 subunits, suggesting expression of PDE6A is essenti

275 at AIPL1 is not involved in the synthesis of PDE6 subunits.

276 ed for the proper assembly of functional rod PDE6 subunits.

277 he proper assembly of synthesized individual PDE6 subunits.

278 ion in levels of rod cGMP phosphodiesterase (PDE6) subunits (alpha, beta, and gamma).

279 Furthermore, assembled phosphodiesterase-6 (PDE6) subunits, rod transducin and G-protein receptor ki

280 ass-specific differences in PDE5 versus cone PDE6 that contribute to the accelerated catalytic effici

281 tify functional differences between PDE5 and PDE6 that will accelerate efforts to develop the next ge

282 we examined the role of distinct isoforms of PDE6, the effector enzyme in phototransduction, in these

283 rminus of Pgamma occludes the active site of PDE6, thereby preventing hydrolysis of cGMP.

284 a regulator of spontaneous activation of rod PDE6, thereby serving to lower rod photoreceptor "dark n

285 cin can stimulate the hydrolytic activity of PDE6 to its maximum extent.

286 involves the binding of isoprenyl groups on PDE6 to the FKBP domain of AIPL1.

287 is responsible for blocking the movement of PDE6 to the outer segment.

288 t amounts of PrBP/delta (<0.1 PrBP/delta per PDE6) to serve as a subunit of PDE6 in either mammalian

289 with its two targets facilitate the alpha(t).PDE6 "transducisome" formation.

290 ents downstream of the Frizzled-2/G alpha t2/PDE6 triad activated in response to Wnt5a, we observed a

291 were eliminated when the beta-subunit of rod PDE6 was removed (Nrl(-/-) cpfl1 rd).

292 tural basis for specific dimerization of rod PDE6, we constructed a series of chimeric proteins betwe

293 of G-protein with Rh* and the activation of PDE6, we investigated the mechanism of the amplification

294 pus laevis is a unique expression system for PDE6 well suited for analysis of the mechanisms of visua

295 e to the accelerated catalytic efficiency of PDE6 were identified but required heterologous expressio

296 in inhibiting other PDE isozymes (PDE1-4 and PDE6) were evaluated.

297 e conformational changes and interactions of PDE6 with known interacting proteins are poorly understo

298 In addition, prolonged incubation of PDE6 with vardenafil or sildenafil (but not 3-isobutyl-1

299 hibitory interaction of phosphodiesterase-6 (PDE6) with its gamma-subunit (Pgamma) is pivotal in vert

300 The interaction of phosphodiesterase 6 (PDE6) with its inhibitory Pgamma-subunits (Pgamma) is un