| Interacting proteins: Q13451 and P04150 |
Pubmed |
SVM Score :0.0 |
| Approximately one half of the GR . hsp90 heterocomplexes in L cell cytosol contains an immunophilin with high affinity FK 506 binding activity , such as FKBP 51 or FKBP 52 , and approximately 35 % contains PP 5 . ^^^ |
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| Interacting proteins: Q13451 and P04150 |
Pubmed |
SVM Score :0.0 |
| Immunoprecipitation experiments distinguished two PR and glucocorticosteroid ( GR ) associated molecular chaperone complexes , containing hsp 90 and hsp 70 and FKBP 52 or FKBP 51 . ^^^ These observations support the concept that FKBP 51 and FKBP 52 can act as regulators of Rap and FK 506 activity upon PR and GR mediated transcription , a mechanism that could be also regulated by type 2 and / or type 4 CaMKs . . ^^^ |
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| Interacting proteins: Q13451 and P04150 |
Pubmed |
SVM Score :0.0 |
| A role for changes in immunophilins , causing glucocorticoid resistance in neotropical primates , is supported by the following : the changes in FKBP 51 and FKBP 52 were observed in cells from other neotropical primates with glucocorticoid resistance ; the elevated level of FKBP 51 was reflected in an abundance of FKBP 51 in heat shock protein 90 complexes in SML ; when cytosols of SML and L 929 cells were mixed , the decrease in GR binding was associated with incorporation of FKBP 51 into GR heterocomplexes ; the effect of SML cytosol on GR binding was reproduced with cytosol from COS cells expressing squirrel monkey FKBP 51 ; and both the effect of SML cytosol on GR binding and the incorporation of FKBP 51 into GR heterocomplexes were blocked by FK 506 . ^^^ Regulation of GR binding by FKBP 51 represents a previously unrecognized mechanism for regulating glucocorticoid sensitivity . . ^^^ |
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| Interacting proteins: Q13451 and P04150 |
Pubmed |
SVM Score :0.0 |
| Squirrel monkey immunophilin FKBP 51 is a potent inhibitor of glucocorticoid receptor binding . ^^^ We have demonstrated that the FK 506 binding immunophilin FKBP 51 is elevated in squirrel monkey lymphocytes ( SML ) and , in preliminary studies , have shown that squirrel monkey FKBP 51 is inhibitory to GR binding . ^^^ In this report , we have demonstrated that elevated FKBP 51 is the unequivocal cause of glucocorticoid resistance in SML in the following ways : 1 ) FK 506 increased GR binding in cytosol from SML in a concentration dependent manner , an effect reproduced by rapamycin but not cyclosporin A . ^^^ The apparent K 6 ( 6 . 1 nM ) and rank order of steroid displacement of [ 3H ] dexamethasone binding in FK 506 treated SML cytosol are characteristic of high affinity GR binding . 2 ) cytosol from COS 7 cells expressing squirrel monkey FKBP 51 inhibited GR binding in cytosol from human lymphocytes by 74 % . ^^^ Cytosol from COS 7 cells expressing human FKBP 51 inhibited GR binding by 23 % . 3 ) expression of squirrel monkey FKBP 51 increased the median effective concentration ( EC 50 ) for dexamethasone in GR transactivation studies in COS 7 cells by approximately 17 fold , compared with the EC 50 in control cells . ^^^ |
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| Interacting proteins: Q13451 and P04150 |
Pubmed |
SVM Score :0.0 |
| Fourth , the relative activities of FKBP 51 from the cotton top tamarin , owl monkey and squirrel monkey were determined in cytosol mixing and GR transactivation studies and showed that FKBP 51 from each of these primates was a potent inhibitor of GR activity . ^^^ |
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| Interacting proteins: Q13451 and P04150 |
Pubmed |
SVM Score :0.0 |
| Rather than causing immediate dissociation of the cytoplasmic GR heterocomplex , binding of hormone induced substitution of one immunophilin ( FKBP 51 ) for another ( FKBP 52 ) , and concomitant recruitment of the transport protein dynein while leaving Hsp 90 unchanged . ^^^ |
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| Interacting proteins: Q13451 and P04150 |
Pubmed |
SVM Score :0.0 |
| Glucocorticoid receptor ( GR ) binding is low in SQMK FP cells because of high expression of the FK 506 binding immunophilin FKBP 51 that inhibits GR binding . ^^^ Glucocorticoid receptor ( GR ) binding is low in SQMK FP cells because of high expression of the FK 506 binding immunophilin FKBP 51 that inhibits GR binding . ^^^ |
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| Interacting proteins: Q13451 and P04150 |
Pubmed |
SVM Score :0.0 |
| Observations of glucocorticoid resistance in New World primates , attributed to FKBP 51 overexpression and incorporation into glucocorticoid receptor complexes , have provided the first evidence that these cochaperones can control hormone binding affinity . ^^^ |
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| Interacting proteins: Q13451 and P04150 |
Pubmed |
SVM Score :0.0 |
| FKBP 51 and FKBP 52 are natural components of glucocorticoid receptor complex and direct regulators of its activity . ^^^ |
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| Interacting proteins: Q13451 and P04150 |
Pubmed |
SVM Score :0.0 |
| We discovered that nuclear translocation of the glucocorticoid receptor was delayed by FKBP 51 . ^^^ The relevance of dynein for receptor function was substantiated by several experiments : 1 ) coexpression of dynamitin , which disrupts the transport complex and reduces receptor activity ; 2 ) coexpression of the PPIase domain fragment of FKBP 52 , which is known to disrupt interaction of the receptor to dynein and reduce glucocorticoid receptor function , in contrast to the corresponding fragment of FKBP 51 ; and 3 ) swapping of the PPIase domains FKBP 51 and FKBP 52 , which reverses the respective activity . ^^^ |
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| Interacting proteins: Q13451 and P04150 |
Pubmed |
SVM Score :0.0 |
| In this work , we have investigated the effects of four TPR proteins ( FKBP 52 , FKBP 51 , Cyp 40 , and PP 5 ) on hormone binding function of glucocorticoid receptor ( GR ) endogenously expressed in mammalian L 929 cells . ^^^ This result correlated with loss of GR associated FKBP 51 and replacement with PP 5 . ^^^ |
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| Interacting proteins: Q13451 and P04150 |
Pubmed |
SVM Score :0.0 |
| To induce apoptosis , GC bind to the GC receptor ( GR ) , which is regulated by various ( co ) chaperone proteins such as heat shock protein 70 ( HSP 70 ) , HSP 40 , HIP ( HSP 70 interacting protein ) , BAG 1 ( BCL 2 associated gene product 1 ) , HOP ( HSP 70 / HSP 90 Organizing protein ) , HSP 90 , P 23 , FKBP 51 , FKBP 52 and CYP 40 . ^^^ |
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| Interacting proteins: Q13451 and P04150 |
Pubmed |
SVM Score :0.0 |
| FK 506 binding protein 51 ( FKBP 51 ) and FKBP 52 are large molecular weight immunophilins that are part of the mature glucocorticoid receptor ( GR ) heterocomplex . ^^^ A naturally occurring animal model of glucocorticoid resistance , the squirrel monkey , results from the relative overexpression of FKBP 51 that renders the GR in a low affinity state . ^^^ The goals of these studies were to determine the roles of the TPR and PPIase domains in the inhibitory activity of squirrel monkey FKBP 51 and to gain insight into structural features of squirrel monkey FKBP 51 responsible for potent inhibition of dexamethasone stimulated GR activity . ^^^ Mutations in the TPR of squirrel monkey FKBP 51 that inhibit association with heat shock protein 90 blocked GR inhibitory activity . ^^^ Mutations that abrogate the PPIase activity of squirrel monkey FKBP 51 had no effect on GR inhibitory activity . ^^^ |
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| Interacting proteins: Q13451 and P04150 |
Pubmed |
SVM Score :0.0 |
| Glucocorticoid resistance in squirrel monkeys results from a combination of a transcriptionally incompetent glucocorticoid receptor and overexpression of the glucocorticoid receptor co chaperone FKBP 51 . ^^^ Glucocorticoid resistance in squirrel monkeys may result from mutations in the glucocorticoid receptor ( GR ) that render it less transcriptionally competent , or expression of the co chaperone FKBP 51 that reduces ligand binding . ^^^ Also , expression of squirrel monkey FKBP 51 reduced responsiveness of both squirrel monkey and human GR in T REx 293 cells . ^^^ The EC ( 50 ) for dexamethasone was 100 fold higher in cells expressing squirrel monkey GR and excess FKBP 51 compared to cells expressing only human GR . ^^^ Overexpression of FKBP 51 in SQMK FP cells had little effect on GR responsiveness , but treatment with FK 506 that blocks the effect of FKBP 51 increased GR responsiveness . ^^^ |
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| Interacting proteins: Q13451 and P04150 |
Pubmed |
SVM Score :0.0 |
| Because neither the PPIase fragment nor the TPR fragment affects the binding of FKBP 52 to the glucocorticoid receptor under conditions in which they block FKBP 52 binding to dynein or hsp 90 , respectively , different regions of FKBP 52 must determine its association with these three proteins . . ^^^ |
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| Interacting proteins: Q13451 and P04150 |
Pubmed |
SVM Score :0.0 |
| Here we show that cotransfection of 3T3 cells with the FKBP 52 PPIase domain and a green fluorescent protein ( GFP ) glucocorticoid receptor ( GR ) chimera inhibits dexamethasone dependent movement of the GFP GR from the cytoplasm to the nucleus . ^^^ After withdrawal of colcemid , microtubules reform , and PPIase inhibition of GFP GR movement is restored . ^^^ Here , we also show that native GR . hsp90 heterocomplexes immunoadsorbed from L cell cytosol contain dynein and that GR . hsp90 heterocomplexes assembled in reticulocyte lysate contain cytoplasmic dynein in a manner that is competed by the PPIase domain of FKBP52 . . ^^^ |
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| Interacting proteins: Q13451 and P04150 |
Pubmed |
SVM Score :0.0 |
| The role of FKBP 52 is to target the GR . hsp90 complex to the nucleus by binding via its PPIase domain to cytoplasmic dynein , the motor protein responsible for retrograde movement along microtubules . ^^^ |
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| Interacting proteins: Q13451 and P04150 |
Pubmed |
SVM Score :0.0 |
| We found significant associations of response to antidepressants and the recurrence of depressive episodes with single nucleotide polymorphisms in FKBP 5 , a glucocorticoid receptor regulating cochaperone of hsp 90 , in two independent samples . ^^^ These single nucleotide polymorphisms were also associated with increased intracellular FKBP 5 protein expression , which triggers adaptive changes in glucocorticoid receptor and , thereby , HPA axis regulation . ^^^ |
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| Interacting proteins: Q13451 and P04150 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13451 and P04150 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13451 and P04150 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13451 and P04150 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13451 and P04150 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13451 and P04150 |
Pubmed |
SVM Score :0.0 |
| NA |
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