ライフサイエンスコーパス: FKBP12

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

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

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

4 nity ternary complexes containing CEP250 and FKBP12.

5 al cytosolic [Ca(2+)], Ca(2+)-calmodulin and FKBP12.

6 bitor rapamycin to the cellular immunophilin FKBP12.

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

8 FKBP) family that is structurally related to FKBP12.

9 novel classes of chemical inhibitors against FKBP12.

10 rubicin, was also significantly inhibited by FKBP12.

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

12 hibits mTOR in complex with the immunophilin FKBP12.

13 ich facilitates interaction with cytoplasmic FKBP12.

14 lective degradation of the cytosolic protein FKBP12.

15 FKBP12.6 cannot be subsequently inhibited by FKBP12.

16 such as the dihydropyridine receptor (DHPR), FKBP12/12.6, and calmodulin (CaM), as well as ions and s

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

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

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

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

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

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

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

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

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

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

27 10% to 20% of endogenous myocyte RyR2s have FKBP12.6 associated, but virtually all myocyte FKBP12.6

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

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

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

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

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

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

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

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

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

37 RISP inhibition, RyR2/FKBP12.6 complex stabilization and Ca(2+) release blocka

38 H, while S107 (a specific stabilizer of RyR2/FKBP12.6 complex) produces an opposite effect.

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

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

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

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

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

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

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

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

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

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

49 FKBP12.6 KO or FK506 treatment enhances CH-induced PH, w

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

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

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

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

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

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

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

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

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

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

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

61 0 binding significantly reduced CaM (but not FKBP12.6) binding to the RyR2.

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

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

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

65 ation of RyR2 by FK506 binding protein 12.6 (FKBP12.6) is decreased in PASMCs from mice with chronic

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

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

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

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

70 The effects of the immunophilins, FKBP12 and FKBP12.6, and phosphorylation on type II ryanodine recep

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

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

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

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

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

76 814 phosphorylation prevents AF induction in FKBP12.6-/- mice by suppressing SR Ca(2+) leak and DADs.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

95 CH causes RISP-dependent ROS generation and FKBP12.6/RyR2 dissociation, leading to PH.

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

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

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

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

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

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

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

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

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

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

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

107 12-kDa FK506- and rapamycin-binding protein (FKBP12, also known as FKBP1A) or the FKBP-rapamycin bind

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

109 s of myocyte surfaces demonstrated that both FKBP12 and 12.6 significantly reduced RyR2 cluster sizes

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

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

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

113 usly expressed immunophilin proteins such as FKBP12 and cyclophilin A.

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

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

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

117 The effects of the immunophilins, FKBP12 and FKBP12.6, and phosphorylation on type II ryan

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

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

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

121 r the rapamycin-mediated association between FKBP12 and FRB, a system relevant in both medicine and c

122 at forms a ternary complex with the proteins FKBP12 and FRB.

123 rapamycin conjugated to specific surfaces on FKBP12 and FRB.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

138 1, calmodulin, and the FK506-binding protein FKBP12, as well as in "hot spot" regions containing site

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

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

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

142 ALK2 free of FKBP12 becomes responsive to the noncanonical inflammato

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

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

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

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

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

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

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

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

151 Sequestration of FKBP12 by rapamycin or tacrolimus activates hepcidin bot

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

153 Thus, FKBP12 can endogenously regulate calcineurin activity wi

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

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

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

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

158 mutations of the A. fumigatus CnA/CnB-FK506-FKBP12-complex identify a Phe88 residue, not conserved i

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

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

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

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

163 FKBP12 deficiency or longer treatments with low dose rap

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

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

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

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

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

169 re, we report the identification of DL001, a FKBP12-dependent rapamycin analog 40x more selective for

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

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

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

173 FKBP12 disruption alone did not cause phenotypic effects

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

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

176 0.15 microM FKBP12 to SR vesicles prevented FKBP12 dissociation; however, in the presence of oxidize

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

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

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

180 recruiting dTAG molecule, to rapidly degrade FKBP12(F36V)-tagged proteins.

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

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

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

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

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

186 ed with FK506 and the FK506-binding protein (FKBP12) from human fungal pathogens (Aspergillus fumigat

187 Although FKBP12 function is well established, its binding determi

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

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

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

191 alphaMyHC-FKBP12 hearts had slower action potential upstrokes and

192 complex, but comparison of fungal and human FKBP12 (hFKBP12) reveals conformational differences in t

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

209 Rapamycin-FKBP12 inhibits the kinase by directly blocking substrat

210 FKBP12 interacts with BMP type I receptors to avoid unco

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

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

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

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

222 gned and synthesized several nanomolar ElteX FKBP12 ligands.

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

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

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

226 The FKBP12-mediated MDM2 degradation was significantly enhan

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

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

229 (38%) of sudden death was found in alphaMyHC-FKBP12 mice.

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

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

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

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

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

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

236 urating concentrations (10 umol/L) of either FKBP12 or 12.6 significantly reduced the frequency, spre

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 irine-based PAL probe for rapamycin, and the FKBP12-photo-rapamycin-FRB ternary complex formed readil

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

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

246 , in complex with the FK506-binding protein (FKBP12), potently and selectively binds the human centro

247 FKBP12 preferentially targets the BMP receptor ALK2.

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

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

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

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

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

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

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

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

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

257 ng protein (FKBP) and circular permutants of FKBP12-rapamycin binding domain (cpFRB).

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

259 The FKBP12-rapamycin complex interferes with TORC1 function

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

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

262 upling interactions dispersed throughout the FKBP12-rapamycin interface.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

278 Whether calcineurin/FKBP12 represents a native physiologically relevant asse

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

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

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

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

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

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

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

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

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

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

289 the latter being distinct from those seen in FKBP12 ternary complexes formed by FK506 and rapamycin.

290 in a bound small molecule can thus reprogram FKBP12 to engage diverse, otherwise "undruggable" target

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

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

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

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

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

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

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

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

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

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