Transglutaminase Activity of Human ER-60

Okudo, Hirokazu; Kito, Makoto; Moriyama, Tatsuya; Ogawa, Tadashi; Urade, Reiko

doi:10.1271/bbb.66.1423

Cited by 8 publications

(3 citation statements)

References 28 publications

(31 reference statements)

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“…IFN-α and IL-15 upregulated both GRP58 mRNA and protein expression in NK-92 cells. GRP58 is a protein chaperone with thiol-dependent protein disulfide isomerase activitiy. − It is involved in chaperoning of many proteins such as MHC class I − and CD1d which are molecules involved in antigen presentation . In addition to chaperone function, GRP58 has been shown to involved in regulation of cell signaling.…”

Section: Discussionmentioning

confidence: 99%

Proteome Characterization of Human NK-92 Cells Identifies Novel IFN-α and IL-15 Target Genes

2004

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Natural killer (NK) cells are important components of innate immune defense. NK cells kill virus-infected cells and secrete cytokines that are involved in activation of other immune cells. Macrophage-derived cytokines interferon-alpha (IFN-alpha) and interleukin-15 (IL-15) are in turn important activators of NK cells, but the receptors and intracellular pathways that are involved in NK cell functions are still incompletely known. Here we have used expression proteomics to find new IFN-alpha and IL-15 regulated proteins in human NK-92 cells, which have the characteristics of activated NK cells. Cells were stimulated with cytokines for 20 h, lysed, and soluble proteins were separated by two-dimensional electrophoresis, and differentially expressed protein spots were identified with mass spectrometry and database searches. A total of 57 protein spots were found to be reproducibly differentially expressed between control and cytokine stimulated gel pairs, 26 spots being more than 2-fold upregulated and 3 spots being at least 2-fold downregulated. The rest 28 spots showed minor, less than 2-fold changes in their expression levels after quantification. From the differentially expressed protein spots we identified 47 different proteins, most of which are new IFN-alpha and IL-15 target proteins. Interestingly, we show that e.g., adenylate kinase 2 is highly upregulated by IFN-alpha and IL-15 stimulation in NK-92 cells. The expression of selected genes with high expression level differences after cytokine stimulation were further studied at mRNA level. Northern blot analysis showed that the genes studied were induced by IFN-alpha, IL-15, and IL-2 already at 3 h time point, suggesting that they are primary target genes of these cytokines.

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Section: Discussionmentioning

confidence: 99%

Proteome Characterization of Human NK-92 Cells Identifies Novel IFN-α and IL-15 Target Genes

2004

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“…It should be noted that other enzymatic activities have been attributed to ERp57, i.e. transglutaminase [22], protease [23] and carnitine palmitoyl transferase [24] activities, although their physiological relevance has not been conclusively assessed. The human protein has been the one most thoroughly investigated.…”

Section: Introductionmentioning

confidence: 99%

ERp57/GRP58: A protein with multiple functions

Turano

Gaucci

Grillo

et al. 2011

Cellular and Molecular Biology Letters

114

108

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Abbreviations used: 1α,25-(OH) 2 D 3 -1α,25-dihydroxycholecalciferol and calcitriol; APE/Ref-1 -apurinic (apyrimidinic) endonuclease/redox-factor 1; CRP -C-reactive protein; ER -endoplasmic reticulum; ERAD endoplasmic reticulum associated protein degradation; mTORC -mammalian target of rapamycin complex; PDI -protein disulfide isomerase; PKC -protein kinases C; PLA 2 -phospholipases A 2 ; Plc -peptide loading complex; PLC -phospholipase C; PrP SC -scrapie prion protein (misfolded prions); STAT -signal transducer and activator of transcription; STAT3 -signal transducer and activator of transcription 3; SV40 virus -simian virus 40; VDR -vitamin D receptor Review ERp57/GRP58: A PROTEIN WITH MULTIPLE FUNCTIONSCARLO TURANO*, ELISA GAUCCI, CATERINA GRILLO and SILVIA CHICHIARELLI Istituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Scienze Biochimiche "A. Rossi Fanelli", Sapienza -Università di Roma, Italy Abstract: The protein ERp57/GRP58 is a stress-responsive protein and a component of the protein disulfide isomerase family. Its functions in the endoplasmic reticulum are well known, concerning mainly the proper folding and quality control of glycoproteins, and participation in the assembly of the major histocompatibility complex class 1. However, ERp57 is present in many other subcellular locations, where it is involved in a variety of functions, primarily suggested by its participation in complexes with other proteins and even with DNA. While in some instances these roles need to be confirmed by further studies, a great number of observations support the participation of ERp57 in signal transduction from the cell surface, in regulatory processes taking place in the nucleus, and in multimeric protein complexes involved in DNA repair.

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“…in the ER. Among them, ER-60 has been shown to be a multifunctional protein, which exhibits disulfide bond isomerase activity (7,16), endoproteinase activity (3,17,18), and transglutaminase-like activity in vitro (19). The isomerase activity of the disulfide bond of ER-60 (ERp57), which may be low compared to that of PDI, has been shown to increase remarkably with addition of the luminal domain of calnexin (CNX), a lectin-type molecular chaperone (20), or calreticulin (CRT), a soluble ER luminal paralog of CNX (21).…”

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confidence: 99%

ER-60 Domains Responsible for Interaction with Calnexin and Calreticulin

et al. 2004

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ER-60 is a thiol oxidoreductase family protein of the endoplasmic reticulum that facilitates the oxidative folding of glycoproteins via interaction with calnexin (CNX) and calreticulin (CRT). In this study, we tried to identify the site of interaction with CNX and CRT in the ER-60 molecule. ER-60 was shown to be composed of at least four domains, named a, b, b', and a', by limited proteolysis. Recombinant fragments of ER-60, a, b', and a'c, were each expressed in Escherichia coli as an individual soluble folded protein that underwent a cooperative unfolding transition along a urea gradient. These fragments each gave the circular dichroism (CD) spectrum of the folded protein. On the other hand, fragment b, which did not undergo the cooperative unfolding transition along a urea gradient gel, did not show any sign of the folded structure on the CD measurement. However, subtraction of the spectra showed that the b domain was folded in wild-type ER-60 or abb'. Both a and a'c, which have a catalytic center CGHC motif, showed activity almost equivalent to half of that of wild-type ER-60. Extension from a or a'c to ab and abb' or b'a'c had little effect on their isomerase activity, suggesting that the b and b' domains hardly contribute to the catalytic activity of ER-60. The contribution of both the b and b' domains to the binding with CNX and CRT was revealed by surface plasmon resonance analysis and oxidative-refolding experiments of monoglucosylated RNase B with addition of the luminal domain of CNX.

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Transglutaminase Activity of Human ER-60

Cited by 8 publications

References 28 publications

Proteome Characterization of Human NK-92 Cells Identifies Novel IFN-α and IL-15 Target Genes

Proteome Characterization of Human NK-92 Cells Identifies Novel IFN-α and IL-15 Target Genes

ERp57/GRP58: A protein with multiple functions

ER-60 Domains Responsible for Interaction with Calnexin and Calreticulin

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