Pubmed abstracts for Protein-Protein Interaction search result :

Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.50472409
As nascent ErbB 2 can associate with both cytoplasmic Hsp 90 and its ER luminal homolog Grp 94 , also a GA binding protein , the purpose of this study was to examine the relative contributions of the cytoplasmic and ER luminal domains of ErbB 2 to the GA sensitivity of the nascent kinase . 0.50472409^^^
Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.98568818
We show that Hsp 90 binds a specific loop within the kinase domain of ErbB 2 , thereby restraining heterodimer formation and catalytic function . 0.98568818^^^
Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.64668455
This reduced the chaperone association of Her 2 with hsp 90 , promoting polyubiquitylation and degradation of Her 2 . 0.64668455^^^
Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
In addition , Hsp 90 family chaperone associated proteins , such as p185erbB2 , Raf 1 , cyclin dependent kinase 4 , and mutant p 53 , were depleted by KF 25706 at a dose comparable to that required for antiproliferative activity . ^^^ KF 29163 , which is an inactive derivative of radicicol , was less potent both in p185erbB2 depletion and Hsp 90 binding . ^^^
Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
BACKGROUND : Heat shock protein 90 ( Hsp 90 ) interacts with and stabilizes several oncogenic protein kinases ( e . g . , p 185 ( erbB 2 ) , p 60 ( 5 src ) , and Raf 1 ) and is required for the stability and dominant negative function of mutated p 53 protein . ^^^
Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
Geldanamycin ( GA ) and herbimycin ( HA ) , specific inhibitors of the cytosolic chaperone HSP 90 and its endoplasmic reticulum homologue GRP 94 , were shown to accelerate degradation of the EGF R and of its homologue p 185 ( c ) ( erbB 2 ) . ^^^
Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
We recently demonstrated that the gyrase inhibitor novobiocin also interacts with Hsp 90 , altering the affinity of the chaperone for geldanamycin and radicicol and causing in vitro and in vivo depletion of key regulatory Hsp 90 dependent kinases including 5 Src , Raf 1 , and p 185 ( ErbB 2 ) . ^^^
Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
The association with Hsp 90 stabilizes key regulatory proteins like Fak , Bcr Abl , ErbB 2 , mutant p 53 and Raf 1 . ^^^
Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
Hsp 90 inhibitory ansamycin antibiotics such as geldanamycin ( GA ) induce rapid ubiquitinylation and down regulation of ErbB 2 . ^^^ Notably , CHIP H260Q induced a dramatic elevation of ErbB 2 association with Hsp 70 and prevented the 17 AAG induced dissociation of Hsp 90 . ^^^
Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
Hsp 90 client proteins include mutated p 53 , Bcr Abl , Raf 1 , Akt , HER2 / Neu ( ErbB 2 ) , and HIF 1alpha . ^^^
Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
Sensitivity of mature Erbb 2 to geldanamycin is conferred by its kinase domain and is mediated by the chaperone protein Hsp 90 . ^^^ Although ErbB 2 and ErbB 1 are highly homologous , they respond quite differently to geldanamycin ( GA ) , an antibiotic that is a specific inhibitor of the chaperone protein Hsp 90 . ^^^ This finding also suggests that the GA sensitivity of mature ErbB 2 depends on cytosolic Hsp 90 , rather than Grp 94 , a homolog of Hsp 90 that is restricted to the lumen of the endoplasmic reticulum , although both chaperones bind to and are inhibited by GA . ^^^ Hsp 90 co immunoprecipitated with all ErbB 2 constructs that were sensitive to GA , but not with ErbB2 / DK or ErbB 1 . ^^^ These data suggest that Hsp 90 uniquely stabilizes ErbB 2 via interaction with its kinase domain and that GA stimulates ErbB 2 degradation secondary to disruption of ErbB2 / Hsp90 association . . ^^^
Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
We also examined inhibition of hsp 90 function and apoptosis induction in erbB 2 overexpressing human breast carcinoma KPL 4 cells in vitro . ^^^ Although the plasma concentrations of these compounds were equivalent , KF 58333 , but not KF 58332 , depleted hsp 90 client proteins such as erbB 2 , raf 1 and Akt in the tumor specimen recovered from nude mice . ^^^
Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
Hsp 90 client proteins include mutated p 53 , Bcr Abl , Raf 1 , Akt , ErbB 2 and hypoxia inducible factor 1 alpha ( HIF 1 alpha ) . ^^^
Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
Western blot and immunoprecipitation techniques were used to analyze expression of cell cycle proteins ( cyclin A , cyclin E , p 53 , and p 21 ) , signaling related proteins ( ErbB 1 , ErbB 2 , and Raf 1 ) , activity of extracellular signal regulated kinase 1 and 2 ( ERK1 / 2 ) , binding of mutant p 53 and Raf 1 to heat shock protein ( Hsp ) 90 , and acetylation of Hsp 90 . ^^^
Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
Geldanamycin ( GA ) , herbimycin A and radicicol bind heat shock protein 90 ( Hsp 90 ) and destabilize its client proteins including 5 Src , Bcr Abl , Raf 1 , ErbB 2 , some growth factor receptors and steroid receptors . ^^^
Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
ErbB 2 overexpression in an ovarian cancer cell line confers sensitivity to the HSP 90 inhibitor geldanamycin . ^^^ In cells overexpressing erbB 2 , the most notable effect on chemosensitivity was that of significantly increased ( 5 fold ) sensitivity to the heat shock protein 90 ( HSP 90 ) molecular chaperone inhibitor geldanamycin . ^^^
Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
Furthermore , in HCT 116 and TA3 / St cells , inhibition of endogenous hyaluronan CD 44 interaction causes disassembly of a constitutive , lipid raft associated , signaling complex containing phosphorylated ErbB 2 , CD 44 , ezrin , phosphoinositide 3 kinase , and the chaperone molecules , Hsp 90 and cdc 37 . ^^^
Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
ERBB 2 increases the sensitivity of breast cancer cells to the HSP 90 inhibitor 17 allylamino 17 demethoxygeldanamycin ( 17 AAG ) . ^^^
Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
A particularly attractive feature of Hsp 90 as a cancer drug target is that it is required for the conformational stability and function of a wide range of oncogenic ' client ' proteins , including c Raf 1 , Cdk 4 , ErbB 2 , mutant p 53 , c Met , Polo 1 and telomerase hTERT . ^^^
Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
Important determinants of response include : 1 ) Dependence upon key HSP 90 client proteins such as ERBB 2 , steroid hormone receptors and AKT / PKB ; 2 ) Levels of HSP 90 family members and co chaperones , such as HSP 70 and AHA 1 ; and 3 ) expression of various cell cycle and apoptotic regulators . ^^^
Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
Among Hsp 90 clients , we focused on ErbB 2 and Bcr Abl as examples of important targets of Hsp 90 inhibitors . ^^^
Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
The achilles heel of ErbB 2 / HER2 : regulation by the Hsp 90 chaperone machine and potential for pharmacological intervention . ^^^ The importance of an Hsp 90 recognition motif located within the kinase domain of ErbB 2 is discussed , as well as a direct role for Hsp 90 in regulating tyrosine kinase activity . ^^^ Hence , the dependence of ErbB 2 upon Hsp 90 reveals an Achilles heel , which opens a window of opportunity for combating cancers driven by the ErbB / HER signaling network . . ^^^
Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
Hsp 90 is overexpressed in cancer cells and is thought to be involved in dealing with the cellular stress associated with malignancy , as well as being essential for a range of key oncogenic proteins , including ErbB 2 , Raf 1 , Akt / PKB , mutant p 53 and many others . ^^^
Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
Targeting hsp 90 by the ansamycins geldanamycin and 17 allyl amino demethoxygeldanamycin ( 17 AAG ) promotes degradation of several proteins through the ubiquitin proteasome pathway , including oncogenic Raf , 5 Src , erbB 2 , and BCR ABL . ^^^
Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
The compounds induce upregulation of HSP 70 and downregulation of the known HSP 90 client proteins Raf 1 , CDK 4 , and ErbB 2 , confirming that the molecules inhibit cell growth by a mechanism dependent on HSP 90 inhibition . ^^^
Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
These models have contrasting implications for how ErbB 2 exerts its biological function and how cancer therapies might down regulate surface ErbB 2 , such as the antibody trastuzumab ( Herceptin ) or the Hsp 90 inhibitor geldanamycin . ^^^
Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
Surface charge and hydrophobicity determine ErbB 2 binding to the Hsp 90 chaperone complex . ^^^ Here we identify a loop within the N lobe of the kinase domain of ErbB 2 that determines Hsp 90 binding . ^^^ A point mutation within the loop that alters ErbB 2 surface properties disrupts Hsp 90 association and confers GA resistance . ^^^ Notably , the immature ErbB 2 point mutant remains sensitive to GA , suggesting that mature and nascent client kinases may use distinct motifs to interact with the Hsp 90 chaperone complex . . ^^^
Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
Here we show that lowering ATP concentration by inhibiting glycolysis or mitochondrial respiration in isolated myocytes triggers rapid dissociation of Hsp 90 from ErbB 2 and degradation of ErbB 2 along with other client proteins . ^^^
Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
The reduction in Hsp 90 was associated with the expression of erbB 2 and erbB 3 in MEXF 276L , while erbB 2 and erbB 3 were absent in the more resistant MEXF 462NL and MEXF 514L cells . ^^^
Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
Treatment of differentiating C2C12 myoblasts with geldanamycin blocked myogenin expression , inhibited myotubule formation , and led to the depletion of three Hsp 90 dependent protein kinases , ErbB 2 , Fyn , and Akt , and induction of apoptosis . ^^^
Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
Hsp 90 client proteins include mutated p 53 , Bcr Abl , Raf 1 , Akt , HER2 / Neu ( ErbB 2 ) and hypoxia inducible factor 1alpha ( HIF 1alpha ) . ^^^
Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
Towards this end , we have investigated the effects of a representative Hsp 90 inhibitor , 17 ( dimethylaminoethylamino ) 17 demethoxygeldanamycin ( 17DMAG ) , on the radiosensitivity of a panel of human tumor cell lines . 17DMAG was previously shown to enhance the radiosensitivity of a number of human cell lines , which correlated with the loss of ErbB 2 . ^^^
Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
Besides androgen receptor , LAQ 824 reduced the level of Hsp 90 client proteins HER 2 ( ErbB 2 ) , Akt / PKB , and Raf 1 in LNCaP cells . ^^^
Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
Hsp 90 inhibitor 17 AAG reduces ErbB 2 levels and inhibits proliferation of the trastuzumab resistant breast tumor cell line JIMT 1 . ^^^ Geldanamycin and its derivative 17 AAG are potential antitumor agents capable of downregulating client proteins of Hsp 90 , including ErbB 2 . ^^^
Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
Hsp 90 binds LIMK 1 via a recognition sequence within the LIMK 1 kinase domain , homologous to that of ErbB 2 . ^^^
Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
The HSP 90 inhibitor 17 allylamino 17 demethoxygeldanamycin ( 17 AAG ) depletes some proteins involved in PI3K / AKT signaling , e . g . , ERBB 2 , epidermal growth factor receptor ( EGFR ) , and phosphorylated AKT ( p AKT ) . 17 AAG and paclitaxel were combined ( at a fixed 1 : 1 ratio of their IC ( 50 ) ) in four ovarian cancer cell lines that differ in expression of p AKT , EGFR , and ERBB 2 . ^^^ The observed effects correlated with changes in the rate of apoptosis induction . 17 AAG induced a decrease in HSP 90 client proteins ( e . g . , C RAF , ERBB 2 , and p AKT ) or in downstream markers of their activity ( e . g . , phosphorylated extracellular signal regulated kinase or p AKT ) in SKOV 3 , IGROV 1 , and CH 1 cells at IC ( 50 ) concentrations . ^^^
Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
Hsp 90 client proteins include telomerase , mutated p 53 , Bcr Abl , Raf 1 , Akt , HER2 / Neu ( ErbB 2 ) , mutated B Raf , mutated EGF receptor , and HIF 1alpha . ^^^
Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
Blockade of Hsp 90 results in reduced cellular levels of several proteins implicated in cancer including CDK 4 , ERBB 2 and C RAF , and causes simultaneous inhibition of cancer cell proliferation in culture and of tumor xenograft growth in vivo . ^^^
Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
A small molecule designed to bind to the adenine nucleotide pocket of Hsp 90 causes Her 2 degradation and the growth arrest and differentiation of breast cancer cells . ^^^ Occupancy of this pocket by several natural products ( geldanamycin ( GM ) and radicicol ) alters Hsp 90 function and results in the degradation of a subset of proteins ( i . e . steroid receptors , Her 2 , Raf ) . ^^^
Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
Development of a purine scaffold novel class of Hsp 90 binders that inhibit the proliferation of cancer cells and induce the degradation of Her 2 tyrosine kinase . ^^^
Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
Hsp 90 clients include several proteins of potential importance in mediating prostate cancer progression , including wild type and mutated AR , HER 2 , and Akt . ^^^
Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
LAQ 824 also induced the acetylation of heat shock protein ( hsp ) 90 , resulting in inhibition of its binding to ATP , which has been shown to impair the chaperone association of hsp 90 with its client proteins , Her 2 , AKT , and c Raf 1 . ^^^ Consistent with this , treatment with LAQ 824 shifted the binding of Her 2 from hsp 90 to hsp 70 , promoting proteasomal degradation of Her 2 . ^^^
Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
Imaging the pharmacodynamics of HER 2 degradation in response to Hsp 90 inhibitors . ^^^ It causes the degradation of HER 2 and other Hsp 90 targets , and has antitumor activity in preclinical models . ^^^
Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
The inhibitory activity of these compounds was determined by their ability to inhibit Hsp 90 ' s inherent ATPase activity along with degradation of the Hsp 90 client protein , HER 2 in MCF 7 breast cancer cells . [ reaction : see text ] . ^^^
Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
Protein degradation assays were performed on Hsp 90 dependent client proteins , Her 2 and Raf , to correlate Hsp 90 inhibition to cytotoxicity . . ^^^
Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
Consistent with the changes in the cellular radiosensitivity , radicicol degraded AR , Raf 1 and HER2 / neu via reduced binding of AR to Hsp 90 , although selective degradation of HER2 / neu caused by Herceptin , a monoclonal antibody against HER 2 , did not affect the cellular radiosensitivity . ^^^
Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
Early tumor response to Hsp 90 therapy using HER 2 PET : comparison with 18F FDG PET . ^^^ We compared ( 68 ) Ga DOTA F ( ab ' ) ( 2 ) herceptin ( DOTA is 1 , 4 , 7 , 10 tetraazacyclododecane N , N ' , N ' ' , N ' ' ' tetraacetic acid [ HER 2 PET ] ) and ( 18 ) F FDG PET for imaging of tumor response to the heat shock protein 90 ( Hsp 90 ) inhibitor 17 allylamino 17 demethoxygeldanamycin ( 17AAG ) . ^^^
Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
Several structurally unrelated HSP 90 inhibitors dose dependently decreased secretion of both IGFBP 2 and HER 2 extracellular domain into culture medium , and both proteins were more sensitive to HSP 90 inhibitors than previously identified biomarkers . ^^^ In addition , we also found that both IGFBP 2 and HER 2 extracellular domain levels are elevated in patient sera from several cancer types , suggesting that these novel secreted biomarkers could be valuable pharmacodynamic tools in clinical trials of HSP 90 inhibitors . . ^^^
Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
Furthermore , the compounds inhibit the growth of the human cancer cell lines SKBR 3 and SKOV 3 , which overexpress Hsp 90 client protein Her 2 , and cause down regulation of Her 2 as well as induction of Hsp 70 consistent with Hsp 90 inhibition . ^^^
Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
Angiogenesis impairment in Id deficient mice cooperates with an Hsp 90 inhibitor to completely suppress HER2 / neu dependent breast tumors . ^^^ The Hsp 90 chaperone protein is required for cellular survival under condition of environmental stress and for the stability of the neu oncogene . 17 Allylamino 17 demethoxygeldanamycin , an Hsp 90 inhibitor , was used to treat these mice . ^^^
Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
The first recombinant antibody fragment , Mycograb ( Neu Tec Pharma plc ) , against Candida HSP 90 is now in clinical trials in patients with disseminated candidiasis in Europe and the US . ^^^
Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
Prominent among the kinases dependent on Hsp 90 is the ErbB family member HER 2 , which is frequently overexpressed in adenocarcinoma and is associated with a poor prognosis and resistance to chemotherapy . ^^^ Disruption of Hsp 90 function promotes the proteasome dependent and ubiquitin mediated degradation of HER 2 , making small molecule chaperone antagonists exciting candidates for clinical development . . ^^^
Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
One of the identified compounds ( G 3130 ) demonstrated cellular activities ( in Her 2 degradation and activation of Hsp 70 promoter ) consistent with the inhibition of cellular Hsp 90 functions . . ^^^
Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P07900	Pubmed	SVM Score :0.0
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