| Interacting proteins: P01266 and P11021 |
Pubmed |
SVM Score :0.60046091 |
| Furthermore , coimmunoprecipitation studies after antimycin A treatment demonstrated that Tg stably associates with BiP , grp 94 , and ERp 72 . 0.60046091^^^ |
|
| Interacting proteins: P01266 and P11021 |
Pubmed |
SVM Score :0.71043393 |
| Moreover , two dimensional gel analysis showed that BiP associated especially well with intracellular Tg containing mispaired disulfide bonds , thought to represent early Tg folding intermediates . 0.71043393^^^ |
|
| Interacting proteins: P01266 and P11021 |
Pubmed |
SVM Score :0.72023362 |
| Interestingly , thapsigargin treatment induces the premature exit of Tg from the calnexin / calreticulin cycle , while stabilizing and prolonging interactions of Tg with BiP ( immunoglobulin heavy chain binding protein ) and GRP 94 ( glucose regulated protein 94 ) , two chaperones whose binding is not carbohydrate dependent . 0.72023362^^^ |
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| Interacting proteins: P01266 and P11021 |
Pubmed |
SVM Score :0.0 |
| Immediately after synthesis , very little Tg associated with calnexin ( a membrane bound molecular chaperone in the ER ) , while a larger fraction bound BiP ( a lumenal ER chaperone ) ; dissociation from these chaperones showed superficially similar kinetics . ^^^ After washout of dithiothreitol , nascent Tg aggregates dissolved intracellularly and were secreted ultimately . 1 h after washout , > or = 92 % of labeled Tg was found to dissociate from calnexin , while the fraction of labeled Tg bound to BiP rose from 0 to approximately 40 % , demonstrating a `` precursor product ' ' relationship . ^^^ |
|
| Interacting proteins: P01266 and P11021 |
Pubmed |
SVM Score :0.0 |
| We have previously demonstrated that several endoplasmic reticulum ( ER ) proteins , including BiP , ERp 72 , grp 94 , and protein disulfide isomerase , bind to a denatured thyroglobulin ( Tg ) affinity column and can be specifically eluted by ATP ( Nigam , S . ^^^ Using chemical cross linking , we now demonstrate that BiP , ERp 72 , and grp 94 associate with Tg in two types of cultured thyroid cells , FRTL 5 and PCC 13 . ^^^ Whereas BiP could be coimmunoprecipitated with anti Tg antibodies in the absence of cross linking , only trace amounts of ERp 72 and grp 94 were coimmunoprecipitated . ^^^ Likewise , in both cell types , anti BiP antibodies were able to coimmunoprecipitate Tg in the absence of cross linking , though ERp 72 and grp 94 were only minimally present . ^^^ Coprecipitation of BiP and Tg was abolished when ATP and Mg2+ were added to cell lysates . ^^^ |
|
| Interacting proteins: P01266 and P11021 |
Pubmed |
SVM Score :0.0 |
| Accelerated dissociation of nascent Tg from the binding protein , BiP , was observed in parallel . ^^^ However , in 4H grown thyrocytes , although there were further increases in ER chaperones , monomer maturation was slowed and the association between nascent Tg and BiP was prolonged . ^^^ |
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| Interacting proteins: P01266 and P11021 |
Pubmed |
SVM Score :0.0 |
| By immunoprecipitation , newly synthesized Tg was associated with the binding protein ( BiP ) ; association was maximal at the earliest chase times . ^^^ Much of the Tg released from BiP by the addition of Mg ATP was found in aggregates containing interchain disulfide bonds ; other BiP associated Tg represented non covalent aggregates and unfolded free monomers . ^^^ Importantly , the immediate precursor to Tg dimer was a compact monomer which did not associate with BiP . ^^^ The average stoichiometry of BiP / Tg interaction involved nearly 10 BiP molecules per Tg molecule . ^^^ |
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| Interacting proteins: P01266 and P11021 |
Pubmed |
SVM Score :0.0 |
| The IRE1p expressing transfectants exhibited a modest ( 2 fold ) enhancement of both the basal and Tg induced level of grp 78 and grp 94 , two coordinately regulated grp genes . ^^^ Using okadaic acid as a specific inhibitor for the endogenous serine / threonine protein phosphatase activities , a mild ( 2 fold ) stimulative effect was observed for Tg induction of grp 78 transcription . ^^^ In contrast , the transcriptional activation of grp 78 by Tg is almost totally eliminated by genistein , a tyrosine kinase inhibitor . ^^^ The grp core , the C 3 and C 1 elements which are major Tg response elements of the rat grp 78 promoter , are also major targets of the inhibitive effects of genistein . . ^^^ |
|
| Interacting proteins: P01266 and P11021 |
Pubmed |
SVM Score :0.0 |
| Chronic TG exposure was also able to induce the expression of GRP 78 . ^^^ The rate of synthesis of GRP 78 , after a lag period of about 2 h , increased gradually to reach a maximum ( 9 fold induction ) after 6 h of TG treatment and was then maintained at that level up to 18 h . ^^^ In both these conditions , by contrast , it was apparent that HT did not affect the TG promoted induction of GRP 78 . ^^^ |
|
| Interacting proteins: P01266 and P11021 |
Pubmed |
SVM Score :0.0 |
| By coimmunoprecipitation in rat thyroid cells , we were able to demonstrate that BiP , grp 94 , ERp 72 , and grp 170 , four proteins believed to function as specific molecular chaperones , complex with Tg during its maturation . ^^^ BiP , grp 94 , and ERp 72 were also found to associate with Tg in cells in which misfolding was induced by perturbing ER calcium stores . ^^^ |
|
| Interacting proteins: P01266 and P11021 |
Pubmed |
SVM Score :0.0 |
| Indeed , non native Tg , GRP 94 , and a 78 kDa protein likely to be BiP , appeared in ternary complexes . ^^^ |
|
| Interacting proteins: P01266 and P11021 |
Pubmed |
SVM Score :0.0 |
| In the present study it was found that the synthesis of the 78 kD glucose regulated protein ( GRP 78 or BIP ) is vigorously induced in human rabdomiosarcoma cells ( TE 671 / RD ) following both short term ( 1 h ) and prolonged ( 18 h ) exposure to 100 nM thapsigargin ( Tg ) . ^^^ Flow cytometric analysis with a specific anti GRP 78 polyclonal antibody showed that Tg treated cells express the GRP 78 on the plasma membrane . ^^^ Cell surface localization of the Tg induced GRP 78 was confirmed by biotinylation of membrane exposed proteins and subsequent isolation of the biotin labelled proteins by streptavidin / agarose affinity chromatography . ^^^ It was found that a fraction of the Tg induced GRP 78 is present among the biotin labelled , surface exposed , proteins . ^^^ Conversely , the GRP 78 immunoprecipitated from unfractionated lysates of Tg treated and biotin reacted cells was found to be biotinylated . ^^^ |
|
| Interacting proteins: P01266 and P11021 |
Pubmed |
SVM Score :0.0 |
| Regarding the colloidal insoluble multimerized Tg ( m Tg ) , which bears dityrosine bridges and is present in the follicular lumen , a mild oxidative system generated different soluble forms of Tg , more or less compacted by hydrophobic associations , and linked with Grp 78 and Grp 94 . ^^^ |
|
| Interacting proteins: P01266 and P11021 |
Pubmed |
SVM Score :0.0 |
| Tg exposure induced 7 . 2 fold , 3 . 6 fold and 8 . 8 fold increase in grp 78 , grp 94 and gadd 153 mRNA levels , respectively . ^^^ However , after peroxide pre exposure , the Tg induced effect on grp 78 , grp 94 and gadd 153 mRNA levels was completely blocked . ^^^ |
|
| Interacting proteins: P01266 and P11021 |
Pubmed |
SVM Score :0.0 |
| Here , we investigated the role of two molecular chaperones , protein disulfide isomerase ( PDI ) and immunoglobulin heavy chain binding protein ( BiP ) , present in the follicular lumen , on the multimerization process due to oxidation using both native Tg and its N terminal domain ( NTD ) . ^^^ Under the same conditions , BiP was able to bind to Tg and NTD multimers but did not affect the process of multimerization . ^^^ |
|
| Interacting proteins: P01266 and P11021 |
Pubmed |
SVM Score :0.0 |
| Exposure of 9L rat brain tumor cells to 300 nM thapsigargin ( TG ) , a sarcoendoplasmic Ca ( 2+ ) ATPases inhibitor , leads to an immediate suppression of general protein synthesis followed by an enhanced synthesis of the 78 kDa glucose regulated protein , GRP 78 . ^^^ TG induced grp 78 expression can be suppressed by the cytosolic free calcium ( [ Ca ( 2+ ) ] ( c ) ) chelator dibromo 1 , 2 bis ( aminophenoxy ) ethane N , N , N ' , N ' tetraacetic acid ( BAPTA ) in a concentration dependent manner . ^^^ Induction of grp 78 is completely abolished in the presence of 20 microM BAPTA under which the TG induced increase of [ Ca ( 2+ ) ] ( c ) is also completely prevented . ^^^ By adding ethyleneglycol bis ( beta aminoethyl ) ether N , N , N ' , N ' tetraacetic acid in the foregoing experiments , in a condition such that endoplasmic reticulum calcium ( [ Ca ( 2+ ) ] ( ER ) ) is depleted and calcium influx from outside is prevented , TG induced grp 78 expression is also abolished . ^^^ These data lead us to conclude that increase in [ Ca ( 2+ ) ] ( c ) , together with the depletion of [ Ca ( 2+ ) ] ( ER ) , are the major causes of TG induced grp 78 expression in 9L rat brain tumor cells . ^^^ |
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| Interacting proteins: P01266 and P11021 |
Pubmed |
SVM Score :0.0 |
| To understand the mechanism of grp 78 induction by ATF 6 in cells subjected to ER calcium depletion stress mediated by thapsigargin ( Tg ) treatment , we discovered that ATF 6 itself undergoes Tg stress induced changes . ^^^ |
|
| Interacting proteins: P01266 and P11021 |
Pubmed |
SVM Score :0.0 |
| We have used thapsigargin ( TG ) , an ER calcium ATPase pump inhibitor that induces calcium release from the ER , to investigate the possible involvement of c Fos , a component of the AP 1 transcription factor , in grp 78 induction . ^^^ Two cell lines with markedly different responses to TG treatment were employed : the WEHI7 . 2 mouse lymphoma line in which TG fails to induce grp 78 , and the MDA MB 468 mammary epithelial line in which TG induces grp 78 . ^^^ In MDA MB 468 cells , TG mediated calcium release induces a sustained elevation of c Fos protein that precedes grp 78 induction . ^^^ In summary , the findings indicate that c Fos is involved in signaling grp 78 induction following TG treatment , and that grp 78 induction is inhibited by proteasome mediated c Fos degradation . . ^^^ |
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| Interacting proteins: P01266 and P11021 |
Pubmed |
SVM Score :0.0 |
| The mRNA levels of genes responding to conditions of ER stress ( grp 78 , grp 94 , gadd 34 and gadd 153 ) were increased up to 200 fold after Tg exposure , whereas those coding for ER resident proteins ( SERCA 2b and Bcl 2 ) were increased up to 6 fold in treated cultures , and those coding for cytoplasmic proteins ( heat shock protein 70 and p 67 ) were increased only 2 4 fold . ^^^ |
|
| Interacting proteins: P01266 and P11021 |
Pubmed |
SVM Score :0.0 |
| Two major trials , the Bezafibrate Infarction Prevention Trial ( BIP ) and the Veterans Affairs High Density Lipoprotein Cholesterol Intervention Trial ( VA HIT ) were conducted to clarify the contribution of correcting diminished high density lipoprotein ( HDL ) ( and lowering triglyceride , TG ) levels to the risk of cardiovascular events in patients with coronary heart disease ( CHD ) . ^^^ However , BIP and VA HIT suggest that correcting HDL and TG levels may be beneficial especially when the LDL level has reached the target value . ^^^ |
|
| Interacting proteins: P01266 and P11021 |
Pubmed |
SVM Score :0.0 |
| Triglyceride ( TG ) accumulation levels of BIP cells were dose dependently inhibited by EDHB and were reduced to 50 % at a 0 . 1 mM concentration . ^^^ |
|
| Interacting proteins: P01266 and P11021 |
Pubmed |
SVM Score :0.0 |
| Through the use of adenoviral vector expression systems , we provide evidence that when ATF 4 function is suppressed and its binding partners are not able to compensate for its function , Grp 78 induction by Tg and Tu is partially inhibited . ^^^ |
|
| Interacting proteins: P01266 and P11021 |
Pubmed |
SVM Score :0.0 |
| A major ER chaperone immunoglobulin binding protein ( BiP ) , and a novel putative escort chaperone endoplasmic reticulum protein 29 KDa ( ERp 29 ) were found to be associated with Tg , which might be interpreted as the contribution of the quality control machinery to the previously shown retention of Tg in the ER . ^^^ |
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| Interacting proteins: P01266 and P11021 |
Pubmed |
SVM Score :0.0 |
| Toward understanding the link between TFII 1 , the tyrosine kinase signaling pathway , and Grp 78 activation , we discovered that Tg stress induces a dramatic increase of TFII 1 phosphorylation at Tyr 248 and localization of this form of TFII 1 to the nucleus . ^^^ We further demonstrate that c Src , which is one of kinases identified to mediate phosphorylation of TFII 1 at Tyr 248 , is activated by Tg stress and is able to stimulate the Grp 78 promoter activity . ^^^ |
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| Interacting proteins: P01266 and P11021 |
Pubmed |
SVM Score :0.0 |
| GRP 78 is specifically induced in cells under the UPR ( unfolded protein response ) , which can be elicited by treatments with calcium ionophore A 23187 and sarcoplasmic / endoplasmic reticulum Ca2+ ATPase inhibitor TG ( thapsigargin ) . ^^^ |
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| Interacting proteins: P01266 and P11021 |
Pubmed |
SVM Score :0.0 |
| An immunoblotting analysis revealed an enhanced expression of GRP 78 , the hallmark of endoplasmic reticulum ( ER ) stress when cells were treated by TG along with BAPTA / AM . ^^^ |
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| Interacting proteins: P01266 and P11021 |
Pubmed |
SVM Score :0.0 |
| When NTG and ATF 6 MER TG mice were treated with or without tamoxifen for 5 days , only the hearts from the tamoxifen treated TG mice exhibited increased levels of many ER stress inducible mRNAs and proteins ; for example , GRP 78 and GRP 94 transcript levels were increased by 8 and 15 fold , respectively . ^^^ |
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| Interacting proteins: P01266 and P11021 |
Pubmed |
SVM Score :0.0 |
| This distribution overlaps that of several Golgi and vesicle markers , including mannosidase 2 , p 58 , trans Golgi network ( TGN ) 38 , and beta COP and is distinct from the endoplasmic reticulum markers calnexin and Bip . ^^^ |
|
| Interacting proteins: P01266 and P11021 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01266 and P11021 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01266 and P11021 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01266 and P11021 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01266 and P11021 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01266 and P11021 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01266 and P11021 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P01266 and P11021 |
Pubmed |
SVM Score :0.0 |
| NA |
|