ライフサイエンスコーパス: FKBP12

1 ans proline isomerase FK506-binding protein (FKBP12).

2 ction with the 12-kDa FK506-binding protein (FKBP12).

3 n bound to the 12 kDa FK506-binding protein (FKBP12).

4 bitor rapamycin to the cellular immunophilin FKBP12.

5 rubicin, was also significantly inhibited by FKBP12.

6 nutlin-3 treated cells was also inhibited by FKBP12.

7 hibits mTOR in complex with the immunophilin FKBP12.

8 y folding of the SH3 domain, cspB, CTL9, and FKBP12.

9 FKBP) family that is structurally related to FKBP12.

10 novel classes of chemical inhibitors against FKBP12.

11 ich facilitates interaction with cytoplasmic FKBP12.

12 oth FKBP12.6 and the closely related isoform FKBP12.

13 lective degradation of the cytosolic protein FKBP12.

14 FKBP12.6 cannot be subsequently inhibited by FKBP12.

15 causes depletion of the stabilizing subunit FKBP12.6 (also known as calstabin2), resulting in leaky

16 RyR2 affinity for the FK506-binding protein FKBP12.6 (Kd~0.8 nmol/L).

17 Our results show that FKBP12.6 activates and FKBP12 inhibits RyR1.

18 In conclusion, FKBP12.6 activates RyR1, whereas FKBP12 activates RyR2 a

19 periments of cardiac SR vesicles with [(35)S]FKBP12.6 also demonstrated that oxidizing reagents decre

20 Exogenous FKBP12.6 also reduced the RyR1 channel P(o) but did not

21 FRET between FKBP12.6 and CaM bound to SR vesicles indicated CaM bind

22 In permeabilized ventricular myocytes, FKBP12.6 and CaM colocalized to Z-lines, and the efficie

23 FK506-binding proteins FKBP12.6 and FKBP12 are associated with cardiac ryanodin

24 Both FKBP12.6 and FKBP12 concentrate at Z-lines, consistent w

25 , whereas RyR2 from other species binds both FKBP12.6 and the closely related isoform FKBP12.

26 10% to 20% of endogenous myocyte RyR2s have FKBP12.6 associated, but virtually all myocyte FKBP12.6

27 channel activity, and disruption of the RyR2-FKBP12.6 association has been implicated in cardiac dise

28 eling at position 41 reduced the affinity of FKBP12.6 binding by 10-fold.

29 rylation site is 105-120 A distance from the FKBP12.6 binding site mapped previously, indicating that

30 mutant RyR2 that is characterized by reduced FKBP12.6 binding to the RyR2 on beta stimulation, the im

31 )O(2) and diamide, result in diminished RyR2-FKBP12.6 binding.

32 Our results show that FKBP12.6 binds to RyR1 and RyR2 in the same orientation

33 The orientation of FKBP12.6 bound to the RyR1 and RyR2 was examined by meas

34 FKBP12.6 but not FKBP12 inhibits basal RyR2 activity.

35 R1 because channels that are preactivated by FKBP12.6 cannot be subsequently inhibited by FKBP12.

36 odine receptors, and competition by untagged FKBP12.6 demonstrated that FKBP12.6-tagged sensors are p

37 9), a drug that has been proposed to prevent FKBP12.6 dissociation from the RyR2 channel complex, did

38 ) nor FK506 (10 mum), a drug which displaces FKBP12.6 from ryanodine receptor 2 (RyR2), had any effec

39 , activation of the CaSR, or displacement of FKBP12.6 from RyR2 for either phase of HPV.

40 Mice lacking RyR2-stabilizing subunit FKBP12.6 had a higher incidence of spontaneous and pacin

41 Neither DPc10 nor FKBP12.6 influences RyR2 binding of the other.

42 However, only FKBP12.6 inhibits resting RyR2 activity.

43 and diamide differentially affected the RyR2-FKBP12.6 interaction, decreasing binding to approximatel

44 FRET mapping of RyR-bound FKBP12.6 is consistent with the predictions of a previou

45 BP12.6 associated, but virtually all myocyte FKBP12.6 is RyR2-bound (because of very high affinity).

46 FKBP12.6 mice exhibit AF caused by SR Ca(2+) leak, Na(+)

47 opposing but different effects of FKBP12 and FKBP12.6 on RyR1 and RyR2 channel gating provide scope f

48 hniques to determine the binding position of FKBP12.6 on the surface of canine RyR2.

49 A cysteine-null mutant FKBP12.6 retained redox-sensitive interaction with RyR2,

50 Overexpression of FKBP12.6 reverted the null phenotype, reducing resting C

51 mic assembly via fluorescent labeling of the FKBP12.6 subunit.

52 RET from the different labeling positions on FKBP12.6 to an acceptor attached within the RyR calmodul

53 ly to be directly involved in the binding of FKBP12.6 to RyR2, as had been proposed previously.

54 teract with binding (and effects) of CaM and FKBP12.6 to RyR2.

55 +)]Cleft-[Ca(2+)]Bulk gradient with GCaMP2.2-FKBP12.6 versus GCaMP2.2, using [Ca(2+)] measured withou

56 he 12-kDa FK506-binding proteins (FKBP12 and FKBP12.6) are regulatory subunits of ryanodine receptor

57 Calmodulin (CaM) and FK506-binding protein (FKBP12.6) bind to RyR2 and stabilize the closed channel.

58 0 binding significantly reduced CaM (but not FKBP12.6) binding to the RyR2.

59 subunit calstabin2 (FK506-binding protein or FKBP12.6) causes SR Ca2+ leak in failing hearts and can

60 RyR2-bound CaM (but not FKBP12.6) drastically slowed DPc10 binding.

61 etion of the stabilizing subunit calstabin2 (FKBP12.6) from the channel complex and intracellular cal

62 Calstabin2 (FKBP12.6) is an RyR2 subunit that stabilizes the closed

63 to the decreased binding of the calstabin2 (FKBP12.6) subunit, which stabilizes the closed state of

64 binding of a 12.6-kDa FK506-binding protein (FKBP12.6) to RyR2, causing a RyR2 malfunction that trigg

65 crease the binding affinity for calstabin-2 (FKBP12.6), a subunit that stabilizes the closed state of

66 bin2, also named FK506 binding protein 12.6 (FKBP12.6), is a subunit of ryanodine receptor subtype 2

67 .6-kDa isoform of the FK506-binding protein (FKBP12.6), whereas RyR2 from other species binds both FK

68 omolecular complex that includes calstabin2 (FKBP12.6).

69 ar myocytes and fluorescently labeled DPc10, FKBP12.6, and CaM.

70 e used site-directed fluorescent labeling of FKBP12.6, ligand binding measurements, and fluorescence

71 asmic reticulum (SR) with recombinant [(35)S]FKBP12.6, we found that the sulfydryl-oxidizing agents,

72 asis of the interaction between Ser-2808 and FKBP12.6, we have employed two independent approaches to

73 Using GCaMP2.2Low-FKBP12.6, we showed that [Ca(2+)]Cleft reaches higher le

74 lower Ca(2+)-affinity variant GCaMP2.2Low to FKBP12.6, which binds with high affinity and selectivity

75 814 phosphorylation prevents AF induction in FKBP12.6-/- mice by suppressing SR Ca(2+) leak and DADs.

76 Atrial myocytes from FKBP12.6-/- mice exhibited spontaneous Ca(2+) waves (SCa

77 s from FKBP12.6-/-:S2814A mice compared with FKBP12.6-/- mice.

78 uced susceptibility to inducible AF, whereas FKBP12.6-/-:S2808A mice were not protected from AF.

79 a(2+) leak, and DADs in atrial myocytes from FKBP12.6-/-:S2814A mice compared with FKBP12.6-/- mice.

80 Moreover, FKBP12.6-/-:S2814A mice exhibited a reduced susceptibili

81 he structural DPc10 binding locus on RyR2 vs FKBP12.6-binding and CaM-binding sites.

82 cent FKBP binding in myocyte revealed a high FKBP12.6-RyR2 affinity (K(d)=0.7+/-0.1 nmol/L) and much

83 horylation of RyR2 was proposed to interrupt FKBP12.6-RyR2 association and activate RyR2.

84 ition by untagged FKBP12.6 demonstrated that FKBP12.6-tagged sensors are positioned to measure local

85 t a single high-affinity site within 60 A of FKBP12.6.

86 ve positions distributed over the surface of FKBP12.6.

87 e converted to the corresponding residues in FKBP12.6.

88 FKBP12 and Gln(31), Asn(32), and Phe(59) in FKBP12.6.

89 behave like FKBP12 and instead behaved like FKBP12.6.

90 at it modulates RyR2 function differently to FKBP12.6.

91 However, the function of FKBP12.6/12 and role of PKA phosphorylation in cardiac m

92 id not alter binding kinetics or affinity of FKBP12.6/12 for RyR2.

93 tricular myocytes, and fluorescently-labeled FKBP12.6/12.

94 on the position of fluorophore attachment on FKBP12.6; however, for any given position, the distance

95 ly 1 micromol/L (similar to [RyR]), whereas [FKBP12.6] is <or=150 nmol/L.

96 nches microsecond-millisecond motions of the FKBP12 80's loop.

97 bitor that also binds FK-binding protein-12 (FKBP12), a repressor of BMP signaling.

98 conclusion, FKBP12.6 activates RyR1, whereas FKBP12 activates RyR2 and this selective activator pheno

99 and (2)H NMR spin relaxation to characterize FKBP12 along the binding coordinate that leads to cell c

100 Mice lacking FKBP12 along the nephron also maintained a normal relati

101 hosphorylated NCC were lower in mice lacking FKBP12 along the nephron than in control mice.

102 minal domain of ribosomal protein L9 (CTL9), FKBP12, alpha-lactalbumin, colicin E7 immunity protein 7

103 itrosylation depleted the channel complex of FKBP12 (also known as calstabin-1, for calcium channel s

104 TOR, raptor (also known as 4932417H02Rik) or FKBP12 (also known as FKBP1A) in antigen-specific CD8 T

105 12-kDa FK506- and rapamycin-binding protein (FKBP12, also known as FKBP1A) or the FKBP-rapamycin bind

106 RCA2, calsequestrin, ryanodine receptor, and FKBP12, although the sodium/calcium exchanger and the L-

107 RapaLink-1 associated with FKBP12, an abundant mTOR-interacting protein, enabling a

108 nation of the functional interaction between FKBP12 and calcineurin, with low doses of the Food and D

109 ble and diblock copolymer ELPs were fused to FKBP12 and characterized with respect to purity, hydrody

110 This "high-dose" drug effect did not require FKBP12 and correlated with an FKBP12-independent suppres

111 omain of ALK2 in complex with the inhibitors FKBP12 and dorsomorphin.

112 The opposing but different effects of FKBP12 and FKBP12.6 on RyR1 and RyR2 channel gating prov

113 The 12-kDa FK506-binding proteins (FKBP12 and FKBP12.6) are regulatory subunits of ryanodin

114 We demonstrate that FKBP12 and FKBP52 catalyze cis/trans isomerization of re

115 malian target of rapamycin pathway proteins (FKBP12 and FRB) that dimerize only in the presence of ra

116 malian target of rapamycin pathway proteins (FKBP12 and FRB) that dimerize only in the presence of ra

117 id residues Glu(31), Asp(32), and Trp(59) in FKBP12 and Gln(31), Asn(32), and Phe(59) in FKBP12.6.

118 /W59F mutant lost all ability to behave like FKBP12 and instead behaved like FKBP12.6.

119 We demonstrate that FKBP12 and its ligands impact multiple aspects of muscle

120 eceptor ALK2 reduce binding of the inhibitor FKBP12 and promote leaky signaling in the absence of lig

121 ine the surfaces of close apposition between FKBP12 and RyR1.

122 ct by serving as an adaptor molecule between FKBP12 and the cell proliferation regulator mTOR (mammal

123 that seen in the ternary complex formed with FKBP12 and the immunosuppressive drug rapamycin; however

124 enates that contained 0.43 microM myoplasmic FKBP12 and was attenuated by S107.

125 the rapamycin-binding site in the absence of FKBP12, and identify a potential new regulatory site tha

126 Rapamycin induces dimerization of the FKBP12- and FRB-containing chimeras; these interactions

127 FK506-binding proteins FKBP12.6 and FKBP12 are associated with cardiac ryanodine receptors (

128 Here, experimental data on the stability of FKBP12 are reported for the effects of three environment

129 s family, and notably FK506 binding protein (FKBP12), are thought to be involved in neurodegenerative

130 We used FKBP12 as a model system and found that in vitro thermod

131 armacologic and genetic studies, we identify FKBP12 as a novel hepcidin regulator.

132 of Molecular Cell, Ahearn et al. identified FKBP12 as a novel regulator of Ras signaling through its

133 1, calmodulin, and the FK506-binding protein FKBP12, as well as in "hot spot" regions containing site

134 we have determined the 3D difference map of FKBP12 associated with RyR1 at 16 A resolution that can

135 We have previously shown that FKBP12 associates with RyR2 in cardiac muscle and that i

136 he rabbit RyR1 in complex with its modulator FKBP12 at an overall resolution of 3.8 A, determined by

137 R leads to incremental rigidification of the FKBP12 backbone on the picosecond-nanosecond timescale.

138 ALK2 free of FKBP12 becomes responsive to the noncanonical inflammato

139 ting structural rearrangements that diminish FKBP12 binding and promote the correct positioning of th

140 binding at a site encompassing the rapamycin-FKBP12 binding domain.

141 cordingly, pulldown analysis and fluorescent FKBP12 binding studies in triadin-null muscles revealed

142 S107 increased FKBP12 binding to RyR1 in SR vesicles in the presence of

143 induction and that FK506-binding protein 12 (FKBP12) binding alone is not adequate to block activatio

144 Meridamycin is a non-immunosuppressive, FKBP12-binding natural macrolide with potential therapeu

145 We show that the prolyl isomerase (PI) FKBP12 binds to H-Ras in a palmitoylation-dependent fash

146 FK506-binding protein 12 (FKBP12) binds the immunosuppressant drugs FK506 and rapa

147 Sequestration of FKBP12 by rapamycin or tacrolimus activates hepcidin bot

148 entire "immunosuppressive complex" including FKBP12, calcineurins A and B, and calmodulin.

149 Thus, FKBP12 can endogenously regulate calcineurin activity wi

150 creating a pocket in which the immunophilin FKBP12 can fit.

151 in-5, enhanced ryanodine binding to the RyR1/FKBP12 complex (EC50 11 microM), however, unexpectedly,

152 The rapamycin.FKBP12 complex inhibits target of rapamycin (TOR) kinase

153 etal muscle function by stabilizing the RyR1-FKBP12 complex.

154 mammals) and its sensitivity to a rapamycin-FKBP12 complex.

155 uscle and nonmuscle cells by modulating RyR1/FKBP12 complex.

156 Both FKBP12.6 and FKBP12 concentrate at Z-lines, consistent with RyR2 and

157 Behaviorally, FKBP12 conditional knockout (cKO) mice displayed enhance

158 HC-FKBP12) mice and cardiomyocyte-restricted FKBP12 conditional knockout (FKBP12(f/f)/alphaMyHC-Cre)

159 The 12 kDa FK506-binding protein (FKBP12) constitutively binds to the calcium release chan

160 estions, we developed a mouse model in which FKBP12 could be deleted along the nephron.

161 FKBP12 deficiency or longer treatments with low dose rap

162 ectrophysiological experiments revealed that FKBP12 deficiency was associated with an enhancement in

163 and in mice with a skeletal muscle-specific FKBP12 deficiency.

164 of exogenous recombinant FKBP12 protein into FKBP12-deficient cardiomyocytes promptly recapitulated a

165 Biochemically, the FKBP12-deficient mice displayed increases in basal mTOR

166 We demonstrate that FKBP12 degrades MDM2 through binding to MDM2 protein, di

167 In single channel measurements with FKBP12-depleted RyR1s, in the absence and presence of NO

168 We demonstrate that fusing an FKBP12-derived destabilizing domain to Cas9 (DD-Cas9) en

169 e E2 DNA binding domain was replaced with an FKBP12-derived domain in which dimerization was regulate

170 FKBP12 disruption alone did not cause phenotypic effects

171 presence of oxidized glutathione and NOC12, FKBP12 dissociation was observed in skeletal muscle homo

172 2), we found that GS domain phosphorylation, FKBP12 dissociation, and disease mutations all destabili

173 0.15 microM FKBP12 to SR vesicles prevented FKBP12 dissociation; however, in the presence of oxidize

174 D40 cytoplasmic region, and 2 ligand-binding FKBP12 domains.

175 Ventricular cardiomyocytes isolated from FKBP12(f/f)/alphaMyHC-Cre hearts showed faster action po

176 cyte-restricted FKBP12 conditional knockout (FKBP12(f/f)/alphaMyHC-Cre) mice and analyzed their cardi

177 FKBP12 (FK506 binding protein 12) is a prolyl cis-trans

178 of FKBP12-rapamycin-binding domain (FRB) and FKBP12 (FK506 binding protein), the interaction of hypox

179 rapamycin-induced FK506 binding protein 12 (FKBP12)-FKBP12 rapamycin binding domain (FRB) associatio

180 scaffold, a fusion of three protein domains, FKBP12, FRB, and GST, presents a peptide linker region f

181 otein pairs (caspase-9-XIAP, caspase-7-XIAP, FKBP12-FRB) and their small molecule modulators.

182 how FK506 is involved in the dissociation of FKBP12 from RyR1.

183 FK506 released FKBP12 from type I receptors activin receptor-like kinas

184 Although FKBP12 function is well established, its binding determi

185 chimera consists of a FK506-binding protein (FKBP12) fused to a cellular 'address' (nuclear localizat

186 d upon rapa-induced translocation of an mRFP-FKBP12 fusion protein that was used as a control.

187 whether the brain-specific disruption of the FKBP12 gene in mice altered mTOR signaling, synaptic pla

188 The FK506- and rapamycin-binding protein (FKBP12) has been the subject of extensive biophysical an

189 alphaMyHC-FKBP12 hearts had slower action potential upstrokes and

190 a modified FK506 binding protein (insertable FKBP12, iFKBP) into the protein kinase isoforms Fyn, Src

191 BEZ235 and partially inhibited by rapamycin/FKBP12 in a noncompetitive fashion toward ATP.

192 that can be fitted with the atomic model of FKBP12 in a unique orientation.

193 These results identify a novel function for FKBP12 in downregulating MDM2, which directly enhances s

194 We have knocked down the expression of FKBP12 in EBV-CTLs using a specific small interfering RN

195 nase activity of mTOR even in the absence of FKBP12 (in the low micromolar range), our most potent li

196 higher binding selectivity for FKBP52 versus FKBP12, in contrast to previously reported immunophilin

197 Inhibitors of FKBP12, in particular, have potent neurotrophic properti

198 ative immunoblots, we determined endogenous [FKBP12] in intact myocytes is approximately 1 micromol/L

199 variety of inhibitors of the PI activity of FKBP12, including FK506, rapamycin, and cycloheximide, i

200 ALK2 mutants defective in binding FKBP12 increase hepcidin expression in a ligand-independ

201 the small FK506 binding protein 12 subunit (FKBP12) increases RyR1 activity and impairs muscle funct

202 e CCI-779 inhibits mTOR signaling through an FKBP12-independent mechanism that leads to profound tran

203 id not require FKBP12 and correlated with an FKBP12-independent suppression of mTOR signaling.

204 Compared to FK506, the fragment-based FKBP12 inhibitors developed herein possess significant a

205 FKBP12.6 but not FKBP12 inhibits basal RyR2 activity.

206 Our results show that FKBP12.6 activates and FKBP12 inhibits RyR1.

207 Rapamycin-FKBP12 inhibits the kinase by directly blocking substrat

208 und critical for the specificity of the RyR1-FKBP12 interaction.

209 FKBP12 interacts with BMP type I receptors to avoid unco

210 The peptidylprolyl isomerase FKBP12 interacts with FK506 forming a complex that inhib

211 Here, we report that FKBP12 interacts with oncoprotein MDM2 and induces MDM2

212 FKBP12 is a critical regulator of I(Na) and is important

213 ree energy of eight FK506-related ligands to FKBP12 is calculated using free energy perturbation mole

214 The FK506-binding protein 12 (FKBP12) is a cytoplasmic protein and has been reported t

215 Fkbp1a (FKBP12) is a ubiquitously expressed cis-trans peptidyl-p

216 all natural product rapamycin, when bound to FKBP12, is a potent inhibitor of an evolutionarily conse

217 It seems as if FKBP12, K201, its dioxole derivative, and 4-MmC inhibit

218 e also created versions of Cas9 fused to the FKBP12-L106P destabilization domain in an effort to impr

219 e calcineurin inhibitor cyclosporine and the FKBP12 ligand rapamycin.

220 to monitor the chemical denaturation of each FKBP12-ligand complex.

221 With GSBP, the size of the simulated FKBP12/ligand systems is significantly reduced, from app

222 We evaluated several new FKBP12 ligands for their ability to stabilize these muta

223 gned and synthesized several nanomolar ElteX FKBP12 ligands.

224 ce and presence of NOC12, S107 augmented the FKBP12-mediated decrease in channel activity.

225 The FKBP12-mediated downregulation of MDM2 in response to do

226 how certain disease-causing mutations bypass FKBP12-mediated kinase inhibition to produce leaky signa

227 The FKBP12-mediated MDM2 degradation was significantly enhan

228 By contrast, FKBP12 mediates spontaneous opening of TRPC1 through iso

229 at the arrhythmogenic phenotype of alphaMyHC-FKBP12 mice is attributable to abnormal I(Na).

230 (38%) of sudden death was found in alphaMyHC-FKBP12 mice.

231 FKBP12 overexpressing transgenic (alphaMyHC-FKBP12) mice and cardiomyocyte-restricted FKBP12 conditi

232 We produced a mutant FKBP12 molecule (FKBP12E31Q/D32N/W59F) where the residue

233 properties and cellular fates of a panel of FKBP12 mutants displaying a range of stabilities when ex

234 lated alterations in I(Na) seen in alphaMyHC-FKBP12 myocytes.

235 In contrast, FKBP12 neither reduced P(o) nor recovered multiple subco

236 The effects of S107 and FKBP12 on RyR1 were examined under conditions that alter

237 s no significant effect on binding of either FKBP12 or 12.6 to RyR2 in myocytes.

238 Mutations in the fkbA gene encoding FKBP12 or the calcineurin cnbR or cnaA genes confer FK50

239 tle effect on other isomerases such as Pin4, FKBP12, or cyclophilin A.

240 12-kDa FK506- and rapamycin-binding protein (FKBP12, or FKBP) and the FKBP-rapamycin binding (FRB) do

241 We generated FKBP12 overexpressing transgenic (alphaMyHC-FKBP12) mice

242 ion for ERalpha (p < 0.01), p53 (p < 0.005), FKBP12 (p < 0.03), ID (p < 0.03), and HDAC1 (p < 0.002).

243 Our results indicate that FKBP12 plays a critical role in the regulation of mTOR-R

244 alpha-syn as a model to interrogate whether FKBP12 plays a role in regulating calcineurin activity i

245 FKBP12 preferentially targets the BMP receptor ALK2.

246 We show that FKBP12 profoundly affects the calcineurin-dependent phos

247 This protein, FKBP12, promotes the RyR1 closed state, thereby inhibiti

248 in of a highly unstable variant of the human FKBP12 protein (ddFKBP).

249 Dialysis of exogenous recombinant FKBP12 protein into FKBP12-deficient cardiomyocytes prom

250 We engineered mutants of the human FKBP12 protein that are rapidly and constitutively degra

251 Moreover, the FKBP12 protein, which stabilizes RyR1 in a closed config

252 in-induced FK506 binding protein 12 (FKBP12)-FKBP12 rapamycin binding domain (FRB) association.

253 When bound to FKBP12, rapamycin interacts with and inhibits the kinase

254 , and rictor (mTORC2) does not interact with FKBP12-rapamycin and is not thought to be rapamycin sens

255 n structures of complexes formed between the FKBP12-rapamycin binding (FRB) domain of mTOR and phosph

256 An FKBP12-rapamycin binding domain (FRB) binding-deficient

257 The FKBP12-rapamycin complex interferes with TORC1 function

258 activity in a manner similar to that of the FKBP12-rapamycin complex.

259 Extended incubation with FKBP12-rapamycin compromises the structural integrity of

260 upling interactions dispersed throughout the FKBP12-rapamycin interface.

261 active site is highly recessed owing to the FKBP12-rapamycin-binding (FRB) domain and an inhibitory

262 otein fused to a fluorescent protein and the FKBP12-rapamycin-binding (FRB) domain from FKBP-12-rapam

263 determinants of TOS recognition, of an mTOR FKBP12-rapamycin-binding (FRB) domain-substrate complex

264 CAs, on the basis of rapamycin modulation of FKBP12-rapamycin-binding domain (FRB) and FKBP12 (FK506

265 e molecular level, the compound binds to the FKBP12-rapamycin-binding domain of mTOR with high affini

266 , a subunit unique to TORC2, is close to the FKBP12-rapamycin-binding domain of Tor2.

267 new assay that involves the expression of an FKBP12-rapamycin-binding domain-tagged candidate vesicle

268 ed dimerization of FK506-binding protein and FKBP12-rapamycin-binding protein.

269 ity, which we conclude is Avo3, occludes the FKBP12-rapamycin-binding site of Tor2's FRB domain rende

270 Removal of this sequence generated a FKBP12-rapamycin-sensitive TORC2 variant, which provides

271 nase (PIKK) family and a signature conserved FKBP12/rapamycin-binding domain.

272 Inhibiting the FKBP12/rapamycin-sensitive subset of mTOR functions in l

273 difies TORC1 and prevents its binding to the FKBP12:rapamycin complex, ultimately leading to rapamyci

274 such that it is no longer able to fully bind FKBP12:rapamycin.

275 containing only the 5-ptase domain fused to FKBP12 rapidly decreased PM PtdIns(4,5)P(2) as monitored

276 These data demonstrate that FKBP12 regulates H-Ras trafficking by promoting depalmit

277 Whether calcineurin/FKBP12 represents a native physiologically relevant asse

278 ur results shed light on the role of several FKBP12 residues that had been found critical for the spe

279 ses cyclophilin A and FK506-binding protein (FKBP12), respectively, block cytokine expression.

280 and the RyR1 stabilizing subunit calstabin1 (FKBP12), resulting in "leaky" channels that cause decrea

281 aza-amides that have been shown to be potent FKBP12 rotamase inhibitors.

282 activity that results in part from impaired FKBP12/RyR1 functional interactions and a secondary incr

283 les revealed a significant impairment of the FKBP12/RyR1 interaction.

284 inity (K(d)=0.7+/-0.1 nmol/L) and much lower FKBP12-RyR2 affinity (K(d)=206+/-70 nmol/L).

285 ssed from a retroviral vector and found that FKBP12-silenced EBV-CTLs are FK506 resistant.

286 cin, in complex with a cytosol protein named FKBP12, specifically inhibits TORC1, causing growth arre

287 ontrol of gene editing in the presence of an FKBP12 synthetic ligand.

288 When we express an FKBP12-tagged ER trap and FRB-tagged Golgi enzymes, cond

289 binding protein (FKBP13) competing with the FKBP12-tagged Golgi enzyme for binding to an FKBP-rapamy

290 Addition of 0.15 microM FKBP12 to SR vesicles prevented FKBP12 dissociation; how

291 Elastin-like Polypeptides (ELPs) fused with FKBP12, to deliver a potent immunosuppressant with dose-

292 d for those amides of FK506-binding protein (FKBP12), ubiquitin, and chymotrypsin inhibitor 2 (CI2) t

293 Removal of FKBP12 using FK506 or rapamycin causes an increased open

294 tage-gated sodium current I(Na) in alphaMyHC-FKBP12 ventricular cardiomyocytes, a slower recovery of

295 B domain of the mammalian target of rapa and FKBP12 was used to translocate a phosphoinositide 5-phos

296 nds, and that of rapamycin in the absence of FKBP12, was investigated by assaying the kinase activity

297 Because MIS releases FK506 binding protein (FKBP12), which activates the mammalian target of rapamyc

298 ges are found with SLF (synthetic ligand for FKBP12, which does not inhibit mTORC1) and in mice with

299 t signals due to the stronger interaction of FKBP12 with R206H.

300 The orientation of RyR1-bound FKBP12, with part of its FK506 binding site facing towar