| Interacting proteins: P42345 and P62942 |
Pubmed |
SVM Score :0.0 |
| The FKBP 12 . rapamycin complex interacts with a recently defined target protein termed the mammalian target of rapamycin ( mTOR ) . ^^^ |
|
| Interacting proteins: P42345 and P62942 |
Pubmed |
SVM Score :0.0 |
| Rapamycin binds intracellularly to the immunophilin FK 506 binding protein 12 ( FKBP 12 ) , and the resultant complex inhibits the protein kinase activity of a protein kinase termed mammalian target of rapamycin ( mTOR ) . ^^^ |
|
| Interacting proteins: P42345 and P62942 |
Pubmed |
SVM Score :0.0 |
| In complex with its cellular receptor , the FK 506 binding protein ( FKBP 12 ) , rapamycin binds and inhibits the function of the mammalian target of rapamycin ( mTOR ) . ^^^ |
|
| Interacting proteins: P42345 and P62942 |
Pubmed |
SVM Score :0.0 |
| Rapamycin inhibits the FK 506 binding protein 12 ( FKBP 12 ) / mammalian target of rapamycin ( mTOR ) complex and causes cell cycle arrest in G 1 . ^^^ |
|
| Interacting proteins: P42345 and P62942 |
Pubmed |
SVM Score :0.0 |
| Rapamycins first bind a cyclophilin FKBP 12 , and this complex binds and inhibits the function of mTOR ( mammalian target of rapamycin ) a serine / threonine ( Ser / Thr ) kinase with homology to phosphatidylinositol 3 ' kinase . ^^^ |
|
| Interacting proteins: P42345 and P62942 |
Pubmed |
SVM Score :0.0 |
| We find that TOR 1 and the mammalian TOR homologue ( mTOR ) also bind FKBP 12 rapamycin , and mutations corresponding to those in TOR 2 similarly block FKBP 12 rapamycin binding . ^^^ |
|
| Interacting proteins: P42345 and P62942 |
Pubmed |
SVM Score :0.0 |
| In this study , we have used a glutathione S transferase ( GST ) FKBP 12 rapamycin affinity matrix to isolate putative mammalian targets of rapamycin ( mTOR ) from tissue extracts . ^^^ Binding experiments performed with rapamycin sensitive and resistant mutant clones derived from the YAC 1 T lymphoma cell line demonstrate that the GST FKBP 12 rapamycin complex recovers significantly lower amounts of the candidate mTOR from rapamycin resistant cell lines . ^^^ Finally , we report the isolation of a full length mTOR cDNA that encodes a direct ligand for the FKBP 12 rapamycin complex . ^^^ These results strongly suggest that the FKBP 12 rapamycin complex interacts with homologous ligands in yeast and mammalian cells and that the loss of mTOR function is directly related to the inhibitory effect of rapamycin on G 1 to S phase progression in T lymphocytes and other sensitive cell types . . ^^^ |
|
| Interacting proteins: P42345 and P62942 |
Pubmed |
SVM Score :0.0 |
| To examine the rate at which the mTOR pathway recovered , the ability of IGF 1 to stimulate p70S6K activity was followed in cells treated for 1 h with rapamycin and then allowed to recover in medium containing > or =100 fold excess of FK 506 ( to prevent rapamycin from rebinding to its cytosolic receptor FKBP 12 ) . ^^^ |
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| Interacting proteins: P42345 and P62942 |
Pubmed |
SVM Score :0.0 |
| RAFT 1 ( rapamycin and FKBP 12 target 1 ; also called FRAP or mTOR ) is a member of the ATM ( ataxia telangiectasia mutated ) related family of proteins and functions as the in vivo mediator of the effects of the immunosuppressant rapamycin and as an important regulator of messenger RNA translation . ^^^ |
|
| Interacting proteins: P42345 and P62942 |
Pubmed |
SVM Score :0.0 |
| The mTOR : FKBP 12 : rapamycin complex blocks G1 / S transition by inhibiting downstream targets essential for cell cycle progression . ^^^ One such target is p70S6k1 ( S6K1 ) , a serine / threonine kinase which is inactivated by the mTOR : FKBP 12 : rapamycin complex , and which has been linked to translational control by virtue of its ability to phosphorylate the ribosomal protein S 6 . ^^^ |
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| Interacting proteins: P42345 and P62942 |
Pubmed |
SVM Score :0.0 |
| Rapamycin inhibits the kinase mTOR , an important regulator of translation , and this inhibition requires binding of the antibiotic to the immunophilin FKBP 12 . ^^^ Displacement of rapamycin from FKBP 12 relieves the inhibition of mTOR and also restores P3k induced transformation . ^^^ |
|
| Interacting proteins: P42345 and P62942 |
Pubmed |
SVM Score :0.0 |
| First , mutations of mTOR or FKBP 12 prevent rapamycin from binding to mTOR , conferring rapamycin resistance . ^^^ |
|
| Interacting proteins: P42345 and P62942 |
Pubmed |
SVM Score :0.0 |
| In essence , RAP gains function by binding to the immunophilin FK 506 binding protein 12 ( FKBP 12 ) and the resultant complex inhibits the activity of mTOR . ^^^ |
|
| Interacting proteins: P42345 and P62942 |
Pubmed |
SVM Score :0.0 |
| Frap ( FKBP 12 rapamycin associated protein , mTOR , RAFT ) was the only gene differing in amino acid sequence between alleles that correlated with strain sensitivity to tumor development . ^^^ |
|
| Interacting proteins: P42345 and P62942 |
Pubmed |
SVM Score :0.0 |
| Rapamycin , in the presence of FKBP 12 , inhibited the association of raptor with mTOR directly in vitro , and concomitantly reduced the mTOR catalysed phosphorylation of raptor dependent , but not raptor independent substrates ; mTOR autophosphorylation was unaltered . ^^^ |
|
| Interacting proteins: P42345 and P62942 |
Pubmed |
SVM Score :0.0 |
| RT PCR showed that the expression of mTOR was suppressed in the HUVECs after rapamycin treatment ; however , FKBP 12 expression was not affected . ^^^ |
|
| Interacting proteins: P42345 and P62942 |
Pubmed |
SVM Score :0.0 |
| Rapamycin is an antineo plastic agent that , in complex with FKBP 12 , is a specific inhibitor of mTOR through interaction with its FKBP 12 rapamycin binding domain , thereby causing G ( 1 ) cell cycle arrest . ^^^ |
|
| Interacting proteins: P42345 and P62942 |
Pubmed |
SVM Score :0.0 |
| In voltage clamped single colonic myocytes rapamycin , which together with FKBP 12 inhibits mTOR ( but not calcineurin ) , decreased the rise in cytosolic Ca2+ concentration ( [ Ca2+ ] c ) evoked by IP3R activation ( by photolysis of caged IP 3 ) , without decreasing the SR luminal Ca2+ concentration ( [ Ca2+ ] l ) as did the mTOR inhibitors RAD 001 and LY 294002 . ^^^ However , FK 506 , which with FKBP 12 inhibits calcineurin ( but not mTOR ) , potentiated the IP 3 evoked [ Ca2+ ] c increase . ^^^ However , FKBP 12 might indirectly modulate Ca2+ release through two effector proteins : ( 1 ) mTOR , which potentiates and ( 2 ) calcineurin , which inhibits Ca2+ release from IP3R in smooth muscle . . ^^^ |
|
| Interacting proteins: P42345 and P62942 |
Pubmed |
SVM Score :0.0 |
| It binds to its intracellular receptor FKBP 12 ( FK 506 binding protein 12 ) , a member of the family of FK 506 binding proteins , and inhibits the activity of mTOR , a serine / threonine kinase involved in numerous cell processes linked to cell growth control . ^^^ |
|
| Interacting proteins: P42345 and P62942 |
Pubmed |
SVM Score :0.0 |
| When bound to FKBP 12 , rapamycin interacts with and inhibits the kinase activity of a multiprotein complex composed of mTOR , mLST 8 , and raptor ( mTORC 1 ) . ^^^ The distinct complex of mTOR , mLST 8 , and rictor ( mTORC 2 ) does not interact with FKBP 12 rapamycin and is not thought to be rapamycin sensitive . mTORC 2 phosphorylates and activates Akt / PKB , a key regulator of cell survival . ^^^ |
|
| Interacting proteins: P42345 and P62942 |
Pubmed |
SVM Score :0.0 |
| The biological activity of the ligands , and that of rapamycin in the absence of FKBP 12 , was investigated by assaying the kinase activity of mTOR . ^^^ While we found that rapamycin binds the FRB domain and inhibits the kinase activity of mTOR even in the absence of FKBP 12 ( in the low micromolar range ) , our most potent ligands bind to FRB with similar binding affinity but inhibit the kinase activity of mTOR at much higher concentrations . ^^^ |
|
| Interacting proteins: P42345 and P62942 |
Pubmed |
SVM Score :0.0 |
| Previously , a mammalian protein that directly associates with FKBP 12 rapamycin has been identified and its encoding gene has been cloned from both human ( designated FRAP ) [ Brown , E . ^^^ Using an in vitro transcription / translation assay method coupled with proteolysis studies , we have identified an 11 kDa FKBP 12 rapamycin binding domain within FRAP . ^^^ |
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| Interacting proteins: P42345 and P62942 |
Pubmed |
SVM Score :0.0 |
| A recently cloned FKBP 12 rapamycin associated protein ( FRAP / RAFT ) is the likely mediator of these effects . ^^^ Using FRAP variants that do not bind FKBP 12 rapamycin , we demonstrate here that FRAP is a rapamycin sensitive regulator of p70S6k in vivo and that the kinase activity of FRAP is required for this regulation . ^^^ Consistent with an essential role for FRAP kinase activity in vivo , autophosphorylation of FRAP is inhibited by FKBP 12 rapamycin . ^^^ |
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| Interacting proteins: P42345 and P62942 |
Pubmed |
SVM Score :0.0 |
| Here we isolate a mammalian FKBP rapamycin associated protein ( FRAP ) whose binding to structural variants of rapamycin complexed to FKBP 12 correlates with the ability of these ligands to inhibit cell cycle progression . ^^^ |
|
| Interacting proteins: P42345 and P62942 |
Pubmed |
SVM Score :0.0 |
| Structure of the FKBP 12 rapamycin complex interacting with the binding domain of human FRAP . ^^^ Rapamycin , a potent immunosuppressive agent , binds two proteins : the FK 506 binding protein ( FKBP 12 ) and the FKBP rapamycin associated protein ( FRAP ) . ^^^ A crystal structure of the ternary complex of human FKBP 12 , rapamycin , and the FKBP 12 rapamycin binding ( FRB ) domain of human FRAP at a resolution of 2 . 7 angstroms revealed the two proteins bound together as a result of the ability of rapamycin to occupy two different hydrophobic binding pockets simultaneously . ^^^ |
|
| Interacting proteins: P42345 and P62942 |
Pubmed |
SVM Score :0.0 |
| FRAP ( FKBP 12 and rapamycin binding protein kinase ) participates in mitogenic and growth factor responses in G 1 and may regulate specific mRNA translation signals . ^^^ |
|
| Interacting proteins: P42345 and P62942 |
Pubmed |
SVM Score :0.0 |
| These proteins , FRAP and FKBP 12 , were synthesized as fusion proteins with Deltaalpha and Deltaomega , respectively . ^^^ |
|
| Interacting proteins: P42345 and P62942 |
Pubmed |
SVM Score :0.0 |
| In the cytoplasm , rapamycin binds to the immunophilin FKBP 12 and the complex of these two molecules binds to a recently discovered protein , FRAP . ^^^ Structure activity studies of rapamycin analogs : evidence that the C 7 methoxy group is part of the effector domain and positioned at the FKBP 12 FRAP interface . ^^^ The rapamycin molecule has two functional domains , defined by their interaction with FKBP 12 ( binding domain ) or with FRAP ( effector domain ) . ^^^ This compound specifically labeled , in an FKBP 12 dependent manner , a protein of approximately 250 kDa , which comigrates with recombinant FRAP . ^^^ |
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| Interacting proteins: P42345 and P62942 |
Pubmed |
SVM Score :0.0 |
| The immunosuppressant rapamycin , in complex with its cellular receptor FKBP 12 , targets the cellular protein FKBP 12 rapamycin associated protein / mammalian target of rapamycin / rapamycin and FKBP 12 target 1 ( FRAP / mTOR / RAFT1 ) and inhibits / delays G 1 cell cycle progression in mammalian cells . ^^^ The FKBP 12 rapamycin binding ( FRB ) domain in FRAP is also speculated to play an important role in FRAP function and signaling . ^^^ |
|
| Interacting proteins: P42345 and P62942 |
Pubmed |
SVM Score :0.0 |
| The cell cycle arrest agent rapamycin binds FK 506 binding protein ( FKBP 12 ) and the FKBP 12 rapamycin binding ( FRB ) domain of FKBP 12 rapamycin associated protein ( FRAP ) simultaneously , and the inhibition of FRAP is responsible for rapamycin ' s biological activity . ^^^ |
|
| Interacting proteins: P42345 and P62942 |
Pubmed |
SVM Score :0.0 |
| The immunosuppressive properties of rapamycin are a result of the formation of the complex FKBP 12 rapamycin FRAP . ^^^ Our objective has been to design biosynthetically available analogues of rapamycin that bind tightly to FKBP 12 but not to FRAP . ^^^ RP 2 and RP 3 have an identical binding affinity ( linear interaction energy calculation ) to FKBP 12 as rapamycin but little or no affinity for binding to FRAP . . ^^^ |
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| Interacting proteins: P42345 and P62942 |
Pubmed |
SVM Score :0.0 |
| Capture of the long lived interaction complex allows the isolation of phage bearing cognate interaction pairs , as we demonstrate for a range of interactions , including Ab antigen pairs and the rapamycin dependent interaction of FKBP 12 and FRAP . ^^^ |
|
| Interacting proteins: P42345 and P62942 |
Pubmed |
SVM Score :0.0 |
| RAFT 1 : a mammalian protein that binds to FKBP 12 in a rapamycin dependent fashion and is homologous to yeast TORs . ^^^ We report that a protein complex containing 245 kDa and 35 kDa components , designated rapamycin and FKBP 12 targets 1 and 2 ( RAFT 1 and RAFT 2 ) , interacts with FKBP 12 in a rapamycin dependent manner . ^^^ We propose that RAFT 1 is the direct target of FKBP 12 rapamycin and a mammalian homolog of the TOR proteins . . ^^^ |
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| Interacting proteins: P42345 and P62942 |
Pubmed |
SVM Score :0.0 |
| We now show that RAFT 1 , immunoprecipitated from rat brain and MG 63 and HEK 293 cells , contains PI 4 kinase activity and that rapamycin FKBP 12 has no effect on this activity . ^^^ |
|
| Interacting proteins: P42345 and P62942 |
Pubmed |
SVM Score :0.0 |
| A mammalian FKBP 12 rapamycin binding protein , RAFT 1 , shares 39 % and 43 % identity with TOR 1 and TOR 2 proteins , respectively but has not been linked to rapamycin action in vivo . ^^^ |
|
| Interacting proteins: P42345 and P62942 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42345 and P62942 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42345 and P62942 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42345 and P62942 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P42345 and P62942 |
Pubmed |
SVM Score :0.0 |
| NA |
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