Calreticulin: A multifunctional protein that is found primarily within membrane-bound organelles. In the ENDOPLASMIC RETICULUM it binds to specific N-linked oligosaccharides found on newly-synthesized proteins and functions as a MOLECULAR CHAPERONE that may play a role in PROTEIN FOLDING or retention and degradation of misfolded proteins. In addition calreticulin is a major storage form for CALCIUM and functions as a calcium-signaling molecule that can regulate intracellular calcium HOMEOSTASIS.Calnexin: A lectin found in ENDOPLASMIC RETICULUM membranes that binds to specific N-linked OLIGOSACCHARIDES found on newly synthesized proteins. It may play role in PROTEIN FOLDING or retention and degradation of misfolded proteins in the endoplasmic reticulum.Ribonucleoproteins: Complexes of RNA-binding proteins with ribonucleic acids (RNA).Calcium-Binding Proteins: Proteins to which calcium ions are bound. They can act as transport proteins, regulator proteins, or activator proteins. They typically contain EF HAND MOTIFS.Endoplasmic Reticulum: A system of cisternae in the CYTOPLASM of many cells. In places the endoplasmic reticulum is continuous with the plasma membrane (CELL MEMBRANE) or outer membrane of the nuclear envelope. If the outer surfaces of the endoplasmic reticulum membranes are coated with ribosomes, the endoplasmic reticulum is said to be rough-surfaced (ENDOPLASMIC RETICULUM, ROUGH); otherwise it is said to be smooth-surfaced (ENDOPLASMIC RETICULUM, SMOOTH). (King & Stansfield, A Dictionary of Genetics, 4th ed)Molecular Chaperones: A family of cellular proteins that mediate the correct assembly or disassembly of polypeptides and their associated ligands. Although they take part in the assembly process, molecular chaperones are not components of the final structures.Calsequestrin: Acidic protein found in SARCOPLASMIC RETICULUM that binds calcium to the extent of 700-900 nmoles/mg. It plays the role of sequestering calcium transported to the interior of the intracellular vesicle.Protein Disulfide-Isomerases: Sulfur-sulfur bond isomerases that catalyze the rearrangement of disulfide bonds within proteins during folding. Specific protein disulfide-isomerase isoenzymes also occur as subunits of PROCOLLAGEN-PROLINE DIOXYGENASE.IndolizinesIsomerases: A class of enzymes that catalyze geometric or structural changes within a molecule to form a single product. The reactions do not involve a net change in the concentrations of compounds other than the substrate and the product.(from Dorland, 28th ed) EC 5.Protein Folding: Processes involved in the formation of TERTIARY PROTEIN STRUCTURE.Lectins: Proteins that share the common characteristic of binding to carbohydrates. Some ANTIBODIES and carbohydrate-metabolizing proteins (ENZYMES) also bind to carbohydrates, however they are not considered lectins. PLANT LECTINS are carbohydrate-binding proteins that have been primarily identified by their hemagglutinating activity (HEMAGGLUTININS). However, a variety of lectins occur in animal species where they serve diverse array of functions through specific carbohydrate recognition.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Calbindin 2: A calbindin protein that is differentially expressed in distinct populations of NEURONS throughout the vertebrate and invertebrate NERVOUS SYSTEM, and modulates intrinsic neuronal excitability and influences LONG-TERM POTENTIATION. It is also found in LUNG, TESTIS, OVARY, KIDNEY, and BREAST, and is expressed in many tumor types found in these tissues. It is often used as an immunohistochemical marker for MESOTHELIOMA.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Congresses as Topic: Conferences, conventions or formal meetings usually attended by delegates representing a special field of interest.Internet: A loose confederation of computer communication networks around the world. The networks that make up the Internet are connected through several backbone networks. The Internet grew out of the US Government ARPAnet project and was designed to facilitate information exchange.Software: Sequential operating programs and data which instruct the functioning of a digital computer.Arthritis, Rheumatoid: A chronic systemic disease, primarily of the joints, marked by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Etiology is unknown, but autoimmune mechanisms have been implicated.Telefacsimile: A telecommunication system combining the transmission of a document scanned at a transmitter, its reconstruction at a receiving station, and its duplication there by a copier.Antirheumatic Agents: Drugs that are used to treat RHEUMATOID ARTHRITIS.Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).Schools, Medical: Educational institutions for individuals specializing in the field of medicine.LondonAlgorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task.Thrombocythemia, Essential: A clinical syndrome characterized by repeated spontaneous hemorrhages and a remarkable increase in the number of circulating platelets.Peptide Termination Factors: Proteins that are involved in the peptide chain termination reaction (PEPTIDE CHAIN TERMINATION, TRANSLATIONAL) on RIBOSOMES. They include codon-specific class-I release factors, which recognize stop signals (TERMINATOR CODON) in the MESSENGER RNA; and codon-nonspecific class-II release factors.Muridae: A family of the order Rodentia containing 250 genera including the two genera Mus (MICE) and Rattus (RATS), from which the laboratory inbred strains are developed. The fifteen subfamilies are SIGMODONTINAE (New World mice and rats), CRICETINAE, Spalacinae, Myospalacinae, Lophiomyinae, ARVICOLINAE, Platacanthomyinae, Nesomyinae, Otomyinae, Rhizomyinae, GERBILLINAE, Dendromurinae, Cricetomyinae, MURINAE (Old World mice and rats), and Hydromyinae.Escherichia coli Proteins: Proteins obtained from ESCHERICHIA COLI.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Escherichia coli: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.Quality Control: A system for verifying and maintaining a desired level of quality in a product or process by careful planning, use of proper equipment, continued inspection, and corrective action as required. (Random House Unabridged Dictionary, 2d ed)Rhode IslandOrganelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the MITOCHONDRIA; the GOLGI APPARATUS; ENDOPLASMIC RETICULUM; LYSOSOMES; PLASTIDS; and VACUOLES.Dihydroorotate Oxidase: An enzyme that in the course of pyrimidine biosynthesis, catalyzes the oxidation of dihydro-orotic acid to orotic acid utilizing oxygen as the electron acceptor. This enzyme is a flavoprotein which contains both FLAVIN-ADENINE DINUCLEOTIDE and FLAVIN MONONUCLEOTIDE as well as iron-sulfur centers. EC 1.3.3.1.Calcium Signaling: Signal transduction mechanisms whereby calcium mobilization (from outside the cell or from intracellular storage pools) to the cytoplasm is triggered by external stimuli. Calcium signals are often seen to propagate as waves, oscillations, spikes, sparks, or puffs. The calcium acts as an intracellular messenger by activating calcium-responsive proteins.Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Sarcoplasmic Reticulum: A network of tubules and sacs in the cytoplasm of SKELETAL MUSCLE FIBERS that assist with muscle contraction and relaxation by releasing and storing calcium ions.Calcium-Transporting ATPases: Cation-transporting proteins that utilize the energy of ATP hydrolysis for the transport of CALCIUM. They differ from CALCIUM CHANNELS which allow calcium to pass through a membrane without the use of energy.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Antibody Specificity: The property of antibodies which enables them to react with some ANTIGENIC DETERMINANTS and not with others. Specificity is dependent on chemical composition, physical forces, and molecular structure at the binding site.Antibodies, Viral: Immunoglobulins produced in response to VIRAL ANTIGENS.Antibodies, Bacterial: Immunoglobulins produced in a response to BACTERIAL ANTIGENS.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Antibody Formation: The production of ANTIBODIES by proliferating and differentiated B-LYMPHOCYTES under stimulation by ANTIGENS.Budd-Chiari Syndrome: A condition in which the hepatic venous outflow is obstructed anywhere from the small HEPATIC VEINS to the junction of the INFERIOR VENA CAVA and the RIGHT ATRIUM. Usually the blockage is extrahepatic and caused by blood clots (THROMBUS) or fibrous webs. Parenchymal FIBROSIS is uncommon.Portal Vein: A short thick vein formed by union of the superior mesenteric vein and the splenic vein.Primary Myelofibrosis: A de novo myeloproliferation arising from an abnormal stem cell. It is characterized by the replacement of bone marrow by fibrous tissue, a process that is mediated by CYTOKINES arising from the abnormal clone.Venous Thrombosis: The formation or presence of a blood clot (THROMBUS) within a vein.Myeloproliferative Disorders: Conditions which cause proliferation of hemopoietically active tissue or of tissue which has embryonic hemopoietic potential. They all involve dysregulation of multipotent MYELOID PROGENITOR CELLS, most often caused by a mutation in the JAK2 PROTEIN TYROSINE KINASE.

Calreticulin, a peptide-binding chaperone of the endoplasmic reticulum, elicits tumor- and peptide-specific immunity. (1/690)

Calreticulin (CRT), a peptide-binding heat shock protein (HSP) of the endoplasmic reticulum (ER), has been shown previously to associate with peptides transported into the ER by transporter associated with antigen processing (Spee, P., and J. Neefjes. 1997. Eur. J. Immunol. 27: 2441-2449). Our studies show that CRT preparations purified from tumors elicit specific immunity to the tumor used as the source of CRT but not to an antigenically distinct tumor. The immunogenicity is attributed to the peptides associated with the CRT molecule and not to the CRT molecule per se. It is further shown that CRT molecules can be complexed in vitro to unglycosylated peptides and used to elicit peptide-specific CD8(+) T cell response in spite of exogenous administration. These characteristics of CRT closely resemble those of HSPs gp96, hsp90, and hsp70, although CRT has no apparent structural homologies to them.  (+info)

Peptide-bound major histocompatibility complex class I molecules associate with tapasin before dissociation from transporter associated with antigen processing. (2/690)

Major histocompatibility complex (MHC) class I molecules present antigenic peptides to CD8 T cells. The peptides are generated in the cytosol, then translocated across the membrane of the endoplasmic reticulum by the transporter associated with antigen processing (TAP). TAP is a trimeric complex consisting of TAP1, TAP2, and tapasin (TAP-A) as indicated for human cells by reciprocal coprecipitation with anti-TAP1/2 and anti-tapasin antibodies, respectively. TAP1 and TAP2 are required for the peptide transport. Tapasin is involved in the association of class I with TAP and in the assembly of class I with peptide. The mechanisms of tapasin function are still unknown. Moreover, there has been no evidence for a murine tapasin analogue, which has led to the suggestion that murine MHC class I binds directly to TAP1/2. In this study, we have cloned the mouse analogue of tapasin. The predicted amino acid sequence showed 78% identity to human tapasin with identical consensus sequences of signal peptide, N-linked glycosylation site, transmembrane domain and double lysine motif. However, there was less homology (47%) found at the predicted cytosolic domain, and in addition, mouse tapasin is 14 amino acids longer than the human analogue at the C terminus. This part of the molecule may determine the species specificity for interaction with MHC class I or TAP1/2. Like human tapasin, mouse tapasin binds both to TAP1/2 and MHC class I. In TAP2-mutated RMA-S cells, both TAP1 and MHC class I were coprecipitated by anti-tapasin antiserum indicative of association of tapasin with TAP1 but not TAP2. With crosslinker-modified peptides and purified microsomes, anti-tapasin coprecipitated both peptide-bound MHC class I and TAP1/2. In contrast, anti-calreticulin only coprecipitated peptide-free MHC class I molecules. This difference in association with peptide-loaded class I suggests that tapasin functions later than calreticulin during MHC class I assembly, and controls peptide loading onto MHC class I molecules in the endoplasmic reticulum.  (+info)

Calreticulin is essential for cardiac development. (3/690)

Calreticulin is a ubiquitous Ca2+ binding protein, located in the endoplasmic reticulum lumen, which has been implicated in many diverse functions including: regulation of intracellular Ca2+ homeostasis, chaperone activity, steroid-mediated gene regulation, and cell adhesion. To understand the physiological function of calreticulin we used gene targeting to create a knockout mouse for calreticulin. Mice homozygous for the calreticulin gene disruption developed omphalocele (failure of absorption of the umbilical hernia) and showed a marked decrease in ventricular wall thickness and deep intertrabecular recesses in the ventricular walls. Transgenic mice expressing a green fluorescent protein reporter gene under the control of the calreticulin promoter were used to show that the calreticulin gene is highly activated in the cardiovascular system during the early stages of cardiac development. Calreticulin protein is also highly expressed in the developing heart, but it is only a minor component of the mature heart. Bradykinin-induced Ca2+ release by the InsP3-dependent pathway was inhibited in crt-/- cells, suggesting that calreticulin plays a role in Ca2+ homeostasis. Calreticulin-deficient cells also exhibited impaired nuclear import of nuclear factor of activated T cell (NF-AT3) transcription factor indicating that calreticulin plays a role in cardiac development as a component of the Ca2+/calcineurin/NF-AT/GATA-4 transcription pathway.  (+info)

Antibody levels to recombinant tick calreticulin increase in humans after exposure to Ixodes scapularis (Say) and are correlated with tick engorgement indices. (4/690)

The antibody responses of subjects who presented with a definite Ixodes scapularis (Say) tick bite were measured to determine the utility of the antibody response against recombinant tick calreticulin (rTC) as a biologic marker of tick exposure. Subjects bitten by I. scapularis evidenced an increase in anti-rTC antibody levels between visit 1 and visit 2 from 24.3 to 27.1 ng/microl serum (n = 88, p = 0.003), and levels remained elevated at visit 3 (p = 0.005). These anti-rTC antibody levels during visits 2 and 3 were significantly higher than those in four non-exposed controls. Tick engorgement indices, measured on the biting ticks, were found to be correlated with anti-rTC antibody levels (e.g., for visit 3: Pearson's r = 0.357, p = 0.001). Tick engorgement index (TEI), ratio of body length to scutal width, was identified to be the only independent predictor of anti-rTC antibody levels in linear regression models. Logistic regression revealed that a bite from an I. scapularis tick that became engorged (TEI >3.4) was a risk factor for anti-rTC antibody seropositivity (adjusted odds ratio for age and bite location = 7.4 (95% confidence interval 2.1-26.4)). The anti-rTC antibody test had a sensitivity of 0.50 and a specificity of 0.86 for a bite from I. scapularis that became engorged. Immunoblotting revealed that subjects made a specific anti-rTC antibody response.  (+info)

Calreticulin expression is associated with androgen regulation of the sensitivity to calcium ionophore-induced apoptosis in LNCaP prostate cancer cells. (5/690)

Calreticulin has been identified previously as one of the androgen-response genes in the prostate. The role of calreticulin in androgen action was studied using androgen-sensitive LNCaP and androgen-insensitive PC-3 human prostate cancer cell lines. Calreticulin appears to be a primary androgen-response gene in cultured LNCaP cells because androgen induction of calreticulin mRNA resists protein synthesis inhibition. Calreticulin is a high capacity intracellular Ca2+ binding protein, suggesting that calreticulin expression is likely to be associated with the intracellular Ca2+ buffering capacity that could regulate the sensitivity to cytotoxic intracellular Ca2+ overload. As expected, androgen protects androgen-sensitive LNCaP but not androgen-insensitive PC-3 cells from cytotoxic intracellular Ca2+ overload induced by Ca2+ ionophore A23187. To provide evidence for the role of calreticulin in reducing cytotoxic effect of Ca2+ influx in prostatic cells, we have shown that calreticulin antisense oligonucleotide down-regulates calreticulin protein level and significantly increases the sensitivity to A23187-induced apoptosis in both LNCaP and PC-3 cells. Furthermore, calreticulin antisense oligonucleotide reverses the androgen-induced resistance to A23187 in LNCaP cells. The above observations collectively suggest that calreticulin mediates androgen regulation of the sensitivity to Ca2+ ionophore-induced apoptosis in LNCaP cells.  (+info)

Ligand-specific, transient interaction between integrins and calreticulin during cell adhesion to extracellular matrix proteins is dependent upon phosphorylation/dephosphorylation events. (6/690)

As transmembrane heterodimers, integrins bind to both extracellular ligands and intracellular proteins. We are currently investigating the interaction between integrins and the intracellular protein calreticulin. A prostatic carcinoma cell line (PC-3) was used to demonstrate that calreticulin can be found in the alpha3 immunoprecipitates of cells plated on collagen type IV, but not when plated on vitronectin. Conversely, alphav immunoprecipitates contained calreticulin only when cells were plated on vitronectin, i. e. not when plated on collagen IV. The interactions between these integrins and calreticulin were independent of actin cytoskeleton assembly and were transient, being maximal approx. 10-30 min after the cells came into contact with the substrates prior to complete cell spreading and formation of firm adhesive contacts. We demonstrate that okadaic acid, an inhibitor of intracellular serine/threonine protein phosphatases, inhibited the alpha3beta1-mediated adhesion of PC-3 cells to collagen IV and the alpha2beta1-mediated attachment of Jurkat cells to collagen I. This inhibition by okadaic acid was accompanied by inhibition of the ligand-specific interaction of calreticulin with the respective integrins in the two cell types. Additionally, we found that pharmacological inhibition of mitogen-activated protein kinase kinase (MEK) resulted in prolongation of the calreticulin-integrin interaction, and enhancement of PC-3 cell attachment to collagen IV. We conclude that calreticulin interacts transiently with integrins during cell attachment and spreading. This interaction depends on receptor occupation, is ligand-specific, and can be modulated by protein phosphatase and MEK activity.  (+info)

Trypanosoma cruzi calreticulin is a lectin that binds monoglucosylated oligosaccharides but not protein moieties of glycoproteins. (7/690)

Trypanosoma cruzi is a protozoan parasite that belongs to an early branch in evolution. Although it lacks several features of the pathway of protein N-glycosylation and oligosaccharide processing present in the endoplasmic reticulum of higher eukaryotes, it displays UDP-Glc:glycoprotein glucosyltransferase and glucosidase II activities. It is herewith reported that this protozoan also expresses a calreticulin-like molecule, the third component of the quality control of glycoprotein folding. No calnexin-encoding gene was detected. Recombinant T. cruzi calreticulin specifically recognized free monoglucosylated high-mannose-type oligosaccharides. Addition of anti-calreticulin serum to extracts obtained from cells pulse-chased with [35S]Met plus [35S]Cys immunoprecipitated two proteins that were identified as calreticulin and the lysosomal proteinase cruzipain (a major soluble glycoprotein). The latter but not the former protein disappeared from immunoprecipitates upon chasing cells. Contrary to what happens in mammalian cells, addition of the glucosidase II inhibitor 1-deoxynojirimycin promoted calreticulin-cruzipain interaction. This result is consistent with the known pathway of protein N-glycosylation and oligosaccharide processing occurring in T. cruzi. A treatment of the calreticulin-cruzipain complexes with endo-beta-N-acetylglucosaminidase H either before or after addition of anti-calreticulin serum completely disrupted calreticulin-cruzipain interaction. In addition, mature monoglucosylated but not unglucosylated cruzipain isolated from lysosomes was found to interact with recombinant calreticulin. It was concluded that the quality control of glycoprotein folding appeared early in evolution, and that T. cruzi calreticulin binds monoglucosylated oligosaccharides but not the protein moiety of cruzipain. Furthermore, evidence is presented indicating that glucosyltransferase glucosylated cruzipain at its last folding stages.  (+info)

Calreticulin affects focal contact-dependent but not close contact-dependent cell-substratum adhesion. (8/690)

We used two cell lines expressing fast (RPEfast) and slow (RPEslow) attachment kinetics to investigate mechanisms of cell-substratum adhesion. We show that the abundance of a cytoskeletal protein, vinculin, is dramatically decreased in RPEfast cells. This coincides with the diminished expression level of an endoplasmic reticulum chaperone, calreticulin. Both protein and mRNA levels for calreticulin and vinculin were decreased in RPEfast cells. After RPEfast cells were transfected with cDNA encoding calreticulin, both the expression of endoplasmic reticulum-resident calreticulin and cytoplasmic vinculin increased. The abundance of other adhesion-related proteins was not affected. RPEfast cells underexpressing calreticulin displayed a dramatic increase in the abundance of total cellular phosphotyrosine suggesting that the effects of calreticulin on cell adhesiveness may involve modulation of the activities of protein tyrosine kinases or phosphatases which may affect the stability of focal contacts. The calreticulin and vinculin underexpressing RPEfast cells lacked extensive focal contacts and adhered weakly but attached fast to the substratum. In contrast, the RPEslow cells that expressed calreticulin and vinculin abundantly developed numerous and prominent focal contacts slowly, but adhered strongly. Thus, while the calreticulin overexpressing RPEslow cells "grip" the substratum with focal contacts, calreticulin underexpressing RPEfast cells use close contacts to "stick" to it.  (+info)

TY - JOUR. T1 - Regulation of calreticulin gene expression by calcium. AU - Waser, Mathilde. AU - Mesaeli, Nasrin. AU - Spencer, Charlotte. AU - Michalak, Marek. PY - 1997/8/11. Y1 - 1997/8/11. N2 - We have isolated and characterized a 12-kb mouse genomic DNA fragment containing the entire calreticulin gene and 2.14 kb of the promoter region. The mouse calreticulin gene consists of nine exons and eight introns, and it spans 4.2 kb of genomic DNA. A 1.8-kb fragment of the calreticulin promoter was subcloned into a reporter gene plasmid containing chloramphenicol acetyltransferase. This construct was then used in transient and stable transfection of NIH/3T3 cells. Treatment of transfected cells either with the Ca2+ ionophore A23187, or with the ER Ca2+-ATPase inhibitor thapsigargin, resulted in a five- to sevenfold increase of the expression of chloramphenicol acetyltransferase protein. Transactivation of the calreticulin promoter was also increased by fourfold in NIH/3T3 cells treated with ...
Buy our Recombinant Human Calreticulin protein. Ab40609 is a protein fragment produced in Escherichia coli and has been validated in SDS-PAGE, MS. Abcam…
Anti-Calreticulin Antibody is an antibody against Calreticulin for use in IC, IH & WB. Find MSDS or SDS, a COA, data sheets and more information.
Although calreticulin (CRT) is a major Ca2+-binding luminal resident protein, it can also appear on the surface of various types of cells and it functions as an immunopotentiating molecule. However, molecular mechanisms underlying the potent immunobiological activity of cell surface CRT are still unclear. In the present study, a recombinant fragment (rCRT/39-272) covering the lectin-like N domain and partial P domain of murine CRT has been expressed in Escherichia coli. The affinity-purified rCRT/39-272 assembles into homodimers and oligomers in solution and exhibits high binding affinity to various glycans, including carrageenan, alginic acids, and hyaluronic acids. Functionally, rCRT/39-272 is capable of driving the activation and maturation of B cells and cytokine production by macrophages in a TLR-4-dependent manner in vitro. It specifically binds recombinant mouse CD14, but not BAFFR and CD40. It is also able to trigger Ig class switching by B cells in the absence of T cell help both in ...
These results show that vasostatin, an NH2-terminal fragment of human calreticulin, can inhibit endothelial cell proliferation in vitro, suppress neovascularization in vivo, and prevent or reduce growth of experimental tumors. Calreticulin, a ubiquitous and highly conserved protein originally identified in skeletal muscle sarcoplasmic reticulum, serves as one of the major storage depots for calcium ions within the endoplasmic reticulum and participates in calcium signaling ((34)-(36)). The NH2-domain of calreticulin, which includes aa 1-180, is the most conserved domain among the calreticulins so far cloned and has no homology to other protein sequences ((34), (35)). Although it does not bind calcium, it can bind the cytoplasmic domain of α subunits of integrins regulating cell attachment ((37)), can interact with the nuclear receptors for glucocorticoid, androgen, and retinoic acid, regulating their binding to DNA ((38)), and can, once phosphorylated, bind stem-loop structures at the 3′-end ...
Calreticulin antibody (calreticulin) for ICC/IF, IHC-P, WB. Anti-Calreticulin pAb (GTX111627) is tested in Human, Mouse, Rat samples. 100% Ab-Assurance.
Abstract Introduction: Calreticulin is a multi-functioning protein located in the endoplasmic reticulum. Several functions have been attributed to calreticulin including lectin-like chaperoning, regulation of gene expression, cell adhesion, auto-immunity and calcium homeostasis. As an endoplasmic reticulum chaperone calreticulin regulates the maturation and folding of several trans-membrane proteins. We hypothesized that as an endoplasmic reticular protein it regulates the expression folding and maturation of epidermal growth factor receptor (EGFR). To date no information is available about the role of calreticulin in EGFR expression and folding. Methods: Wild type calreticulin deficient (crt -/-) and mouse lung cancer cells isolated from transgenic mice over expressing calreticulin was used to examine the expression, localization and function of EGFR. Western blot analysis was used to determine the protein expression. Immunocytochemical staining of cells was utilized to determine localization of EGFR
Ca2+ release in saponin-permeabilized calreticulin-deficient cells. Wild-type (K41) and calreticulin-deficient (K42) cells were loaded with a fluorescent Ca2+ i
Blockade of the checkpoint inhibitor programmed death 1 (PD1) has demonstrated remarkable success in the clinic for the treatment of cancer; however, a majority of tumors are resistant to anti-PD1 monotherapy. Numerous ongoing clinical combination therapy studies will likely reveal additional therapeutics that complement anti-PD1 blockade. Recent studies found that immunogenic cell death (ICD) improves T cell responses against different tumors, thus indicating that ICD may further augment antitumor immunity elicited by anti-PD1. Here, we observed antitumor activity following combinatorial therapy with anti-PD1 Ab and the cyclin-dependent kinase inhibitor dinaciclib in immunocompetent mouse tumor models. Dinaciclib induced a type I IFN gene signature within the tumor, leading us to hypothesize that dinaciclib potentiates the effects of anti-PD1 by eliciting ICD. Indeed, tumor cells treated with dinaciclib showed the hallmarks of ICD including surface calreticulin expression and release of high ...
Quality control of the endoplasmic reticulum plays a critical role in protein folding, modification and modification of a secretory pathway. As endoplasmic reticulum chaperones, calreticulin and calnexin have similar substrate specificity and share several common features. Yet, surprisingly, mice bearing a disruption in the calreticulin gene die from a lesion in cardiac development and develop significant metabolic problems whereas calnexin-deficient mice are born alive with, yet not understood, neurological problems. Studies with calreticulin and calnexin gene knockout mice and calreticulin- and calnexindeficient cell lines indicate that calnexin is unable to compensate for the loss of calreticulin and conversely, calreticulin cannot compensate for the loss of calnexin. Calreticulin or calnexin deficiency or reduction in the level of ERp57 protein (ERp57 heterozygote mice) leads to development of metabolic disorders as documented by sever changes serum lipids and carbohydrates composition in ...
Accumulating evidence is revealing the essential role of immune system in cancer treatment. Certain chemotherapeutic drugs can potently induce the release of cell death associated molecular patterns (CDAMPs), which accompanies cancer cell demise. CDAMPs can engage corresponding receptors on immune cells and stimulate immune responses to achieve long-term tumor control (Ma et al., 2013; Ma et al., 2014; Yang et al., 2015). Among reported CDAMPs, calreticulin (CALR), ATP and HMGB1 are well known for their immune-stimulatory effect. Here we describe the assays that we applied to measure cell death and these CDAMPs. Briefly, cell death can be analyzed by co-staining of 4,6-diamidino-2-phenylindole (DAPI) with 3,3-Dihexyloxacarbocyanine Iodide [DiOC6(3)] or Annexin V. CALR exposure on the cell membrane can be detected by flow cytometry. ATP and HMGB1 release can be quantified by luminescence assay and ELISA assay respectively.
TY - JOUR. T1 - Evolving Evidence of Calreticulin as a Pharmacological Target in Neurological Disorders. AU - Kotian, Vignesh. AU - Sarmah, Deepaneeta. AU - Kaur, Harpreet. AU - Kesharwani, Radhika. AU - Verma, Geetesh. AU - Mounica, Leela. AU - Veeresh, Pabbala. AU - Kalia, Kiran. AU - Borah, Anupom. AU - Wang, Xin. AU - Dave, Kunjan R. AU - Yavagal, Dileep R. AU - Bhattacharya, Pallab. PY - 2019/1/1. Y1 - 2019/1/1. N2 - Calreticulin (CALR), a lectin-like ER chaperone, was initially known only for its housekeeping function, but today it is recognized for many versatile roles in different compartments of a cell. Apart from canonical roles in protein folding and calcium homeostasis, it performs a variety of noncanonical roles, mostly in CNS development. In the past, studies have linked Calreticulin with various other biological components which are detrimental in deciding the fate of neurons. Many neurological disorders that differ in their etiology are commonly associated with aberrant levels of ...
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This family of GBPs is widespread in evolution and plays a key role in ER quality control,ref name=Ellgaard 2003a,Ellgaard, L. and Frickel, E. M. Calnexin, calreticulin, and ERp57: teammates in glycoprotein folding. Cell Biochem Biophys 39, 223-247 (2003),/ref,,ref name=Jorgensen 2003,Jorgensen, M. M., Bross, P. and Gregersen, N. Protein quality control in the endoplasmic reticulum. APMIS Suppl 86-91 (2003),/ref,,ref name=Ellgaard 2003,Ellgaard, L. and Helenius, A. Quality control in the endoplasmic reticulum. Nat Rev Mol Cell Biol 4, 181-191 (2003),/ref,,ref name=Helenius 2004,Helenius, A. and Aebi, M. Roles of N-linked glycans in the endoplasmic reticulum. Annu Rev Biochem 73, 1019-1049 (2004),/ref,,ref,Molinari, M., Eriksson, K. K., Calanca, V., Galli, C., Cresswell, P., Michalak, M. and Helenius, A. Contrasting functions of calreticulin and calnexin in glycoprotein folding and ER quality control. Mol Cell 13, 125-135 (2004),/ref,,ref,Deprez, P., Gautschi, M. and Helenius, A. More ...
Does anyone have an antibody to human calreticulin that they can let us have for work on rheumatoid arthritis? Thanks Frank -- Frank C Hay Division of Immunology St Georges Hospital Medical School London SW17 0RE, UK Tel: 0181 767 5751 Fax: 0181 725 3549 email: frank at rabbits.demon.co.uk ...
Calreticulin: A multifunctional protein that is found primarily within membrane-bound organelles. In the ENDOPLASMIC RETICULUM it binds to specific N-linked oligosaccharides found on newly-synthesized proteins and functions as a MOLECULAR CHAPERONE that may play a role in PROTEIN FOLDING or retention and degradation of misfolded proteins. In addition calreticulin is a major storage form for CALCIUM and functions as a calcium-signaling molecule that can regulate intracellular calcium HOMEOSTASIS.
Actual Exams Sales Cloud Consultant training service - Salesforce CRT-251 online test materials with real CRT-251 practice exam questions.
The present study contains novel findings supporting the concept that ICD can be induced by chemotherapy alone in patients with breast cancer and ESCC. Firstly, both HMGB1 and calreticulin expression were significantly upregulated after NAC. Secondly, chemotherapeutic drugs induced the upregulation of HMGB1 and calreticulin in several tested breast cancer cell lines.. We and others have recently reported that danger signals from dying cells following treatment with radiotherapy or certain chemotherapeutic drugs, such as anthracyclines and oxaliplatin, can induce Toll-like receptor (TLR)-dependent, antigen-specific T-cell immunity (22,23). Additional therapeutic modalities shown to induce ICD include oncolytic virus therapy (24-26) and photodynamic therapy (27,28). Furthermore, among various danger signals released from dying cells in a tumor-bearing mouse model, HMGB1, but not other known TLR4 ligands, could be a mandatory factor to induce tumor antigen-specific T-cell immunity (22,23). ...
The present study contains novel findings to support the concept of immunogenic cell death induced by chemoradiotherapy in patients with ESCC. First, tumor antigen-specific T-cell responses were confirmed in 6 (38%) of 16 patients with ESCC following chemoradiotherapy. Second, the serum level of HMGB1 following chemoradiation in the patients with antigen-specific T-cell responses was significantly elevated in comparison to that in the patients without antigen-specific T-cell responses. Third, upregulation of HMGB1 within tumor microenvironments was significantly related to preoperative chemoradiotherapy and the degree of HMGB1 positively correlated with patients survival. Fourth, both irradiation and chemodrugs could induce upregulation of HMGB1 and calreticulin on ESCC cell lines in vitro. Finally, HMGB1 was able to induce maturation of DCs in an in vitro culture system.. In general, chemoradiotherapy is thought to induce an immunosuppressive state in both T-cell and natural killer-cell ...
Dear All Please read attached document for details of 4th international CALRETICULIN workshop to be held at Oxford University in April 2000 If you have problems opening the attachment or are worried about viruses look at our homepage on:- http://www.uwcm.ac.uk/uwcm/mb/crt2000.html Yours sincerely, Paul Eggleton. Dept Biochemistry. University of Oxford. UK ...
Researchers at Juntendo University report in the journal Leukemia how mutants of the protein calreticulin lead to molecular mechanisms triggering myeloproliferative neoplasms, which can cause cancer. The findings may lead to the development of novel therapies for certain types of blood cancer.
Two key factors that mediate high-glucose-induced downregulation of the glucose transport system in bovine aortic endothelial cells and in the human-derived EA.hy926 cells have been identified: the lipid peroxidation product 4-HDDE and its cognate nuclear receptor PPARδ. The latter increases the expression of the protein calreticulin that was shown before to destabilize GLUT-1 mRNA (13).. The augmented production of 4-HDDE results from high-glucose-induced 12-LO expression and activity and glucose-derived ROS. The mechanism responsible for the increased expression of 12-LO is not yet known. Numerous studies have proven that hyperglycemia promotes the generation of ROS (3,7). We showed before an augmented production of ROS in bovine aortic endothelial cell primary cultures under high-glucose conditions (28). Two observations confirm the role of ROS in the generation of 4-HDDE from 12-LO metabolites. First, the inhibition of 12-LO activity with baicalein significantly reduced 4-HDDE secretion ...
The term immunogenic cell death (ICD) denotes an immunologically unique type of regulated cell death that enables, rather than suppresses, T cell-driven immune responses that are specific for antigens derived from the dying cells. The ability of ICD to elicit adaptive immunity heavily relies on the immunogenicity of dying cells, implying that such cells must encode and present antigens not covered by central tolerance (antigenicity), and deliver immunostimulatory molecules such as damage-associated molecular patterns and cytokines (adjuvanticity). Moreover, the host immune system must be equipped to detect the antigenicity and adjuvanticity of dying cells. As cancer (but not normal) cells express several antigens not covered by central tolerance, they can be driven into ICD by some therapeutic agents, including (but not limited to) chemotherapeutics of the anthracycline family, oxaliplatin and bortezomib, as well as radiation therapy. In this Trial Watch, we describe current trends in the ...
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Nangalia J., Massie C.E., Baxter E.J., Nice F.L., Gundem G., Wedge D.C., Avezov E., Li J., Kollmann K., Kent D.G., Aziz A., Godfrey A.L., Hinton J., Martincorena I., Van Loo P., Jones A.V., Guglielmelli P., Tarpey P., Harding H.P., Fitzpatrick J.D., Goudie C.T., Ortmann C.A., Loughran S.J., Raine K., Jones D.R., Butler A.P., Teague J.W., OMeara S., McLaren S., Bianchi M., Silber Y., Dimitropoulou D., Bloxham D., Mudie L., Maddison M., Robinson B., Keohane C., Maclean C., Hill K., Orchard K., Tauro S., Du M.-Q., Greaves M., Bowen D., Huntly B.J.P., Harrison C.N., Cross N.C.P., Ron D., Vannucchi A.M., Papaemmanuil E., Campbell P.J., Green A.R., Somatic CALR Mutations in Myeloproliferative Neoplasms with Nonmutated JAK2, 10.1056/nejmoa1312542 ...
p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.,/p> ,p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.,/p> ,p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).,/p> ,p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x,sup>64,/sup> + x,sup>4,/sup> + x,sup>3,/sup> + x + 1. The algorithm is described in the ISO 3309 standard. ,/p> ,p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.,br /> ,strong>Cyclic redundancy and other checksums,/strong>,br /> ,a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993),/a>),/p> Checksum:i ...
Genetic variation at the chromosome 9p21 risk locus promotes cardiovascular disease; however, it is unclear how or which proteins encoded at this locus contribute to disease. We have previously demonstrated that loss of one candidate gene at this locus, cyclin-dependent kinase inhibitor 2B (Cdkn2b), in mice promotes vascular SMC apoptosis and aneurysm progression. Here, we investigated the role of Cdnk2b in atherogenesis and found that in a mouse model of atherosclerosis, deletion of Cdnk2b promoted advanced development of atherosclerotic plaques composed of large necrotic cores. Furthermore, human carriers of the 9p21 risk allele had reduced expression of CDKN2B in atherosclerotic plaques, which was associated with impaired expression of calreticulin, a ligand required for activation of engulfment receptors on phagocytic cells. As a result of decreased calreticulin, CDKN2B-deficient apoptotic bodies were resistant to efferocytosis and not efficiently cleared by neighboring macrophages. These ...
Lead: Tim Illidge. Radiation treatment (RT) is a highly effective anti-cancer treatment that is delivered to over 50% of all cancer patients and 40% of those cured of their disease.. In order to further improve cancer outcomes using RT, an increased understanding of what determines effective RT-induced anti-tumour responses and how best to combine RT with others treatments is required.. Our research programme evaluates the contribution of RT-induced immunogenic cell death to the induction of tumour-specific immune responses (Project 1); determines how best to integrate RT with immunomodulatory agents to augment such responses and enhance therapeutic outcome (Project 2); and investigates how combination with RT and immune modulation can be utilised to increase the efficacy and durability of anti-CD20 mAb therapy in B- cell lymphomas (Project 3).. The pre-clinical experimental programme runs in parallel with early phase clinical trials to form a cohesive and overlapping programme of work that aims ...
CALR antibody - C-terminal region (ARP30114_P050) | Application: WB | CALR is strongly supported by BioGPS gene expression data to be expressed in Human HepG2 cells | Alias: RO; CRT; SSA; cC1qR
Overexpression of the conserved Ca2+-binding proteins calreticulin and calsequestrin impairs cardiac function, leading to premature death. Calreticulin is vital for embryonic development, but also impairs glucocorticoid action. Glucocorticoid overexposure during late fetal life causes intra-uterine growth retardation and programmed hypertension in adulthood. To determine whether intra-uterine growth retardation or programmed hypertension was associated with altered calreticulin or calsequestrin expression, effects of prenatal glucocorticoid overexposure (maternal dexamethasone treatment on days 15-21 of pregnancy) were examined during fetal life and postnatal development until adulthood (24 weeks). Dexamethasone (100 or 200μg/kg of maternal body weight) was administered via osmotic pump. Calreticulin was detected as a 55kDa band and calsequestrin as 55 and 63kDa bands in 21 day fetal hearts. Only the 55kDa calsequestrin band was detected postnatally. Prenatal glucocorticoid overexposure at the ...
Immunogenic cell death (ICD) is associated with the emission of so-called damage-associated molecular patterns (DAMPs) which trigger the immune response against dead-cell associated antigens. The secretion of the DAMP, adenosine triphosphate (ATP) has been shown to be autophagy-dependent. Here, we demonstrate that Modified Vaccinia virus Ankara (MVA), a highly attenuated strain of vaccinia virus, induces both cell death and autophagy in murine bone marrow-derived dendritic cells (BMDCs), which in turn confer the (cross-)priming of OVA-specific cytotoxic T cells (OT-I cells). Additionally, we show that MVA infection leads to increased extracellular ATP (eATP) as well as intracellular ATP (iATP) levels, with the latter being influenced by the autophagy. Furthermore, we show that the increased eATP supports the proliferation of OT-I cells and inhibition of the P2RX7 receptors results in an abrogation of the proliferation. These data reveal novel mechanisms on how MVA enhances adaptive immunity in ...
We have proposed that rTcCRT [13, 14] provides an important at least partial explanation of why T. cruzi experimental infection or the inoculation of parasite extracts exerts toxic effects on different tumor types, mammary adenocarcinoma among them (reviewed in [2]).. We have described a 45 kDa T. cruzi, highly pleiotropic chaperone protein, TcCRT [13]. rTcCRT [13] is antiangiogenic because it inhibits ECs proliferation, migration and morphogenesis, in several in vitro, ex vivo and in vivo assays, in 3 species, H. s. sapiens included [9, 16, 17]. Furthermore, in vivo, rTcCRT inhibits the growth of an experimental mammary adenocarcinoma, when inoculated in an area near the tumor. This effect is more potent than the one elicited by its rHuCRT counterpart [9]. However, the proposal that T.cruzi infection has an antitumor effect mediated by its nTcCRT, needs a formal demonstration, as justified in the Introduction section. This important question was addressed herein. In order to causally implicate ...
The surface exposure of CRT and ERp57 was increased in CT26 clones derived from cells transiently exposed to nocodazole that contained close to twice the DNA content of parental cells (which we refer to as "hyperploid" cells), although the surface expression of most other membrane proteins was unaltered (Fig. 1D and fig. S8). This hyperploidy-associated increase in CRT exposure was also observed in mouse Lewis lung carcinoma (LLC) and fibrosarcoma MCA205 cells, as well as in human cancer cell lines (fig. S9). As compared to their parental counterparts, hyperploid clones exhibited constitutive PERK and eIF2α phosphorylation (Fig. 1E). Interruption of the CRT exposure pathway reduced the clonogenic potential of hyperploid cells (Fig. 1, F and G), suggesting a functional link between the ER stress-associated CRT exposure pathway and the fitness of hyperploid cells.. Because hyperploidization is linked to CRT exposure, we wondered whether cancer cells with increased DNA content might be subjected ...
The surface exposure of CRT and ERp57 was increased in CT26 clones derived from cells transiently exposed to nocodazole that contained close to twice the DNA content of parental cells (which we refer to as "hyperploid" cells), although the surface expression of most other membrane proteins was unaltered (Fig. 1D and fig. S8). This hyperploidy-associated increase in CRT exposure was also observed in mouse Lewis lung carcinoma (LLC) and fibrosarcoma MCA205 cells, as well as in human cancer cell lines (fig. S9). As compared to their parental counterparts, hyperploid clones exhibited constitutive PERK and eIF2α phosphorylation (Fig. 1E). Interruption of the CRT exposure pathway reduced the clonogenic potential of hyperploid cells (Fig. 1, F and G), suggesting a functional link between the ER stress-associated CRT exposure pathway and the fitness of hyperploid cells.. Because hyperploidization is linked to CRT exposure, we wondered whether cancer cells with increased DNA content might be subjected ...
In this study, we determined the subcellular accumulation of HTLV-1 p12I to further define the possible function for this protein in viral infection. We demonstrate that p12I is retained as a membrane-associated protein and is expressed predominantly in the ER and cis-Golgi apparatus. Two regions of the protein containing predicted transmembrane domains are independently responsible for this pattern of localization. Importantly, we are the first to identify the interaction of p12I with both calreticulin and calnexin in the ER, suggesting a possible function of the viral protein in calcium-mediated cell signaling leading to host cell activation. These findings are consistent with our previous studies that demonstrated a requirement for HTLV-1 p12I in viral infectivity both in a rabbit model of infection (12), in primary lymphocytes in vitro (1), and in calcium-dependent nuclear factor of activated T cells-mediated transcription (B. Albrecht et al., unpublished data).. HTLV-1 p12I is highly ...
Veysel Sabri Han er, H seyin Tokg z, Serkan G ven , mran al kan, Murat B y kdo an. Three Novel Calreticulin Mutations in Two Turkish Patients. Turk J Hematol. 2017; 34(4): 360- ...
In the present study we demonstrate, using arthritis models, that TFM-C, a celecoxib analogue with 205-fold lower COX-2-inhibitory activity, inhibits autoimmune disease. TFM-C differs from celecoxib by the substitution of the 4-methyl group by a trifluoromethyl group. This substitution drastically increases the IC50s for inhibition of COX1 (15 μM to ,100 μM for celecoxib and TFM-C, respectively) and COX2 (0.04 μM to 8.2 μM, respectively), but does not affect the apoptotic index measured in PC3 prostate cancer cells, indicating independence between structural requirements for COX-2 inhibition and apoptosis induction [36]. Celecoxib perturbs intracellular calcium by blocking ER Ca2+ ATPases, and this activity is shared with TFM-C [23, 37]. In a HEK293 recombinant cell system, this Ca2+ perturbation is associated with inhibition of secretion and altered intracellular interaction of IL-12 polypeptide chains with the ER chaperones calreticulin and ERp44, and results in the interception of IL-12 ...
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New treatments for triple-negative breast cancer (TNBC) are urgently needed. Despite there being little evidence of clinical activity as single-agent therapies, we show that dual blockade of PI3Kα and CDK4/6 is synergistically effective against multiple RB1-wild-type TNBC models. Combined PI3Kα and CDK4/6 inhibition significantly increased apoptosis, cell-cycle arrest, and tumor immunogenicity and generated immunogenic cell death in human TNBC cell lines. Combination treatment also significantly improved disease control in human xenograft models compared with either monotherapy. Combined PI3Kα and CDK4/6 inhibition significantly increased tumor-infiltrating T-cell activation and cytotoxicity and decreased the frequency of immunosuppressive myeloid-derived suppressor cells in a syngeneic TNBC mouse model. Notably, combined PI3Kα and CDK4/6 inhibition, along with inhibition of immune checkpoints PD-1 and CTLA-4, induced complete and durable regressions (,1 year) of established TNBC tumors in ...
NBTXR3 exposed to irradiation enhanced cancer cells destruction and immunogenic cell death compared to irradiation alone, suggesting a strong potential for transforming tumor into an effective in situ vaccine. This may contribute to transform "cold" tumor into "hot" tumor and effectively be combined with most of the immunotherapeutic agents across oncology. NBTXR3 is intended to be injected in the tumors. Spilling in the circulation may occur during product administration or, as expected, during tumor destruction, leading to steady trapping of NPs in the reticulo-endothelial system (liver and spleen). Clinically, it is unknown whether patients, previously treated with NPs, may show toxic signs when NPs are exposed (activation) to diagnosis imaging (computed tomography(CT)) of the liver.. Continuer la lecture…. ...
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Protein folding in the endoplasmic reticulum (ER) is error prone, and ER quality control (ERQC) processes ensure that only correctly folded proteins are exported from the ER. Glycoproteins can be retained in the ER by ERQC, and this retention contributes to multiple human diseases, termed ER storage diseases. UDP-glucose:glycoprotein glucosyltransferase (UGGT1) acts as a central component of glycoprotein ERQC, monoglucosylating deglucosylated N-glycans of incompletely folded glycoproteins and promoting subsequent reassociation with the lectin-like chaperones calreticulin and calnexin. The extent to which UGGT1 influences glycoprotein folding, however, has only been investigated for a few selected substrates. Using mouse embryonic fibroblasts lacking UGGT1 or those with UGGT1 complementation, we investigated the effect of monoglucosylation on the soluble/insoluble distribution of two misfolded alpha 1-antitrypsin (AAT) variants responsible for AAT deficiency disease: null Hong Kong (NHK) and Z ...
Endoplasmic-reticulum-associated protein degradation (ERAD) designates a cellular pathway which targets misfolded proteins of the endoplasmic reticulum for ubiquitination and subsequent degradation by a protein-degrading complex, called the proteasome. The process of ERAD can be divided into three steps: The recognition of misfolded or mutated proteins depends on the detection of substructures within proteins such as exposed hydrophobic regions, unpaired cysteine residues and immature glycans. In mammalian cells for example, there exists a mechanism called glycan processing. In this mechanism, the lectin-type chaperones calnexin/calreticulin (CNX/CRT) provide immature glycoproteins the opportunity to reach their native conformation. They can do this by way of reglucosylating these glycoproteins by an enzyme called UDP-glucose-glycoprotein glucosyltransferase. Terminally misfolded proteins, however, must be extracted from CNX/CRT. This is carried out by members of the EDEM (ER ...
The peptide-loading complex (PLC) is a transient, multisubunit membrane complex in the endoplasmic reticulum that is essential for establishing a hierarchical immune response. The PLC coordinates peptide translocation into the endoplasmic reticulum with loading and editing of major histocompatibility complex class I (MHC-I) molecules. After final proofreading in the PLC, stable peptide-MHC-I complexes are released to the cell surface to evoke a T-cell response against infected or malignant cells. Sampling of different MHC-I allomorphs requires the precise coordination of seven different subunits in a single macromolecular assembly, including the transporter associated with antigen processing (TAP1 and TAP2, jointly referred to as TAP), the oxidoreductase ERp57, the MHC-I heterodimer, and the chaperones tapasin and calreticulin ...
Figure 2: LTX-315 induces immunogenic cell death in cancer cells. When treated with LTX-315, dying cancer cells release damage-associated molecular patterns (DAMP) such as calreticulin, ATP, HMGB1, mitochondria-derived DNA (mtDNA) and formyl peptides (FMIT). DAMPs bind to specific receptors on antigen-presenting cells such as dendritic cells (DC) and promotes their maturation and engulfment of tumor-antigens with subsequent presentation to T cells and execution of effective immune response (Zhou et al, and Eike et al, Oncotarget, 2015, Zhou et al, Cell Death and Disease, 2016, Sveinbjørnsson et al, Future Medicinal Chemistry, 2017) ...
Methods: The study included primary cultures of CAFs isolated from freshly resected NSCLC (n = 7) and freshly isolated Peripheral Blood Mononuclear Cells (PBMCs) isolated from randomly selected healthy volunteers. A potential crosstalk between irradiated or non-irradiated CAFs and T-lymphocytes was examined using in vitro co-cultures and PBMCs exposed to CAF-conditioned medium (CM). Relevant cell functions were analyzed by a series of assays including lymphocyte proliferation assays, lymphocyte migration assays, Treg assays and T-cell cytokine production. In the search for mechanisms behind the observed effects, a series of molecular assays including multiplex protein arrays, ELISAs, LC-MS/MS proteomics and cytokines specific blocking assays were performed. Finally the induction of immunogenic cell death (ICD) of CAFs in response to HD-RT (1 x 18 Gy) was studied by examining the release of high motility group box 1 (HMGB1) and ATP into the extracellular space ...
We have recently identified (a) ectocalreticulin as the main source of immunogenicity of cancer cell death induced by chemotherapy or radiotherapy, (b) ectoERP57 as critical protein for inducing cell surface exposure of calreticulin, and (c) that ectoERP57 and ectocalreticulin are cotranslocated together to the tumor cell surface by the mediator of the inhibition of PP1/GADD34 complex. Here, I report that the immunogenicity of cancer cell death induced by anticancer targeted proapoptotic peptides is also dictated by ectocalreticulin. To improve the anticancer activity of these proapoptotic peptides, I have designed several targeted chimeric inhibitor peptides of the PP1/GADD34 complex, which are comprised of an inhibitor peptide of the PP1/GADD34 complex fused to a protein transduction domain-5, to prostate homing peptide, or to the tumor antigen BiP/GRP78-binding peptide motifs. These inhibitor peptides (a) induce ectocalreticulin and ectoERP57 in a variety of tumor cell lines by the mediator ...
SIL1 antibody [N1N3] (SIL1 homolog, endoplasmic reticulum chaperone (S. cerevisiae)) for IHC-P, WB. Anti-SIL1 pAb (GTX116755) is tested in Human, Rat samples. 100% Ab-Assurance.
... Lumenal domain of calnexin from PDB 1JHN. Available structures: 1jhn Identifiers Symbol(s) CANX; CNX; FLJ26570; IP90; P90 External IDs
Hep I stimulates association of LRP with the Gαi2 subunit, and association is blocked by RAP and by peptides corresponding to the COOH terminus of Gαi2. (A) BAE cells were grown to near confluence and serum deprived overnight. Cells were then treated with 1 μM hep I for 0, 5, 10, 15, or 30 min and lysed. Cell lysates were immunoprecipitated with monoclonal anti-LRP antibody (8G1), separated by SDS-PAGE, and immunoblotted with mouse anti-Gαi2 antibodies. A representative immunoblot for LRP-associated Gαi2 is shown. Bands were analyzed using One-Dscan software (Scanalytics), and the fold change in LRP-Gαi2 association as compared with untreated conditions was determined. Equal loading of sample protein was assessed by protein staining with Ponceau S. *, P , 0.05; **, P , 0.01 (n = 3-5). (B) BAE cells were grown as in A, treated for 10 min with either DMEM, 100 nM hep I, 78 nM TSP, or 100 nM modified hep I and assayed for LRP-Gαi2 association as described in A. A representative immunoblot ...
We studied the role of the recently identified CALR mutations in 141 patients with Budd-Chiari Syndrome (BCS) or portal vein thrombosis (PVT) in a large multinational cohort. A CALR mutation was present in one of the 141 patients (0.7%). This patient was previously diagnosed with primary myelofibrosis. This results in CALR positivity in one out of 44 (2.3%) patients with myeloproliferative neoplasm (MPN), and in one of 11 (9.1%) JAK2V617F negative patients diagnosed with MPN. We suggest that analysis of CALR mutations should be performed in JAK2V617F negative BCS and PVT patients.. BCS and non-malignant, non-cirrhotic PVT are rare vascular liver diseases. The etiology of these diseases encompasses both inherited and acquired risk factors, of which MPN are the most common with a prevalence ranging between 20%-50%.1-3 Detecting presence of MPN in patients with BCS and PVT is important, given the prognostic and potential therapeutic implications regarding anticoagulant therapy.4,5 However, ...
Looking for online definition of Calcium Homeostasis Endoplasmic Reticulum Protein in the Medical Dictionary? Calcium Homeostasis Endoplasmic Reticulum Protein explanation free. What is Calcium Homeostasis Endoplasmic Reticulum Protein? Meaning of Calcium Homeostasis Endoplasmic Reticulum Protein medical term. What does Calcium Homeostasis Endoplasmic Reticulum Protein mean?
The biogenesis of nascent proteins translocated into the calcium‐rich, oxidizing milieu of the endoplasmic reticulum (ER) lumen is assisted by a group of resident ER proteins that include molecular chaperones and folding enzymes. These specialized ER proteins are constitutively expressed in all cells, where they play a role in monitoring and assisting the maturation of normal proteins (Gething and Sambrook, 1992; Hendrick and Hartl, 1993) and are essential for proper steady‐state operations of the eukaryotic secretory pathway. Expression of mutant secretory pathway proteins or exposure of cells to agents that adversely affect ER protein folding and maturation all result in the accumulation of unfolded proteins in the ER, thereby activating an inter‐organelle signaling pathway linking the ER and nucleus. This response, termed the unfolded protein response (UPR), includes the coordinate transcriptional up‐regulation of ER chaperones and folding enzymes (Lee, 1992).. In yeast, an ER ...
N-Glycans are modified as part of a quality control mechanism during glycoprotein folding in the endoplasmic reticulum (ER). Glucosidase II (GII) plays a critical role by generating monoglucosylated glycans that are recognized by lectin chaperones, calnexin and calreticulin. To understand how the hydrolytic activity of GIIα is enhanced by the mannose 6-phosphate receptor (MPR) homology domain (MRH domain) of its β subunit, we now report a 1.6 Å resolution crystal structure of the MRH domain of GIIβ bound to mannose. A comparison of ligand-bound and unbound structures reveals no major difference in their overall fold, but rather a repositioning of side chains throughout the binding pocket, including Y372. Mutation of Y372 inhibits GII activity, demonstrating an important role for Y372 in regulating GII activity. Comparison of the MRH domains of GIIβ, MPRs, and the ER lectin OS-9 identified conserved residues that are critical for the structural integrity and architecture of the carbohydrate ...
def: "A protein complex that is located in the endoplasmic reticulum and is composed of chaperone proteins, including BiP, GRP94; CaBP1, protein disulfide isomerase (PDI), ERdj3, cyclophilin B, ERp72, GRP170, UDP-glucosyltransferase, and SDF2-L1." [PMID:12475965 ...
Multiple myeloma (MM), a bone marrow-resident hematological malignancy of plasma cells, has remained largely incurable despite dramatic improvements in patient outcomes in the era of myeloma-targeted and immunomodulatory agents. It has recently become clear that T cells from MM patients are able to recognize and eliminate myeloma, although this is subverted in the majority of patients who eventually succumb to progressive disease. T cell exhaustion and a suppressive bone marrow microenvironment have been implicated in disease progression, and once these are established, immunotherapy appears largely ineffective. Autologous stem cell transplantation (ASCT) is a standard of care in eligible patients and results in immune effects beyond cytoreduction, including lymphodepletion, T cell priming via immunogenic cell death, and inflammation; all occur within the context of a disrupted bone marrow microenvironment. Recent studies suggest that ASCT reestablishes immune equilibrium and thus represents a ...
Researchers at the Max Planck Institute, Goethe University and Martin Luther University are deciphering the structure of the MHC-I peptide-loading complex.
In this study, we have identified two unique aspects of STIM1 function that are separate but overlapping. We discovered that ERp57, an ER‐resident oxidoreductase, interacts with the ER luminal domain of STIM1 and affects SOC. Although ERp57−/− cells show reduced ER Ca2+ stores, expression of ERp57 in ERp57−/− cells inhibits SOC without restoring Ca2+ stores, supporting a role for ERp57 on SOC by interaction with STIM1 rather than its effects on the size of ER Ca2+ stores. ERp57/STIM1 interaction involves two conserved cysteines (C49 and C56), forming a disulphide bridge upstream from the EF‐hand domain. The mutation of these residues to eliminate the disulphide bond rendered STIM1 incapable of proper punctae translocation. As the conserved C49 and C56 are located in close proximity to the EF‐hand Ca2+ sensor in STIM1, these results indicated that the conformation of the disulphide‐containing region of STIM1 might affect that of the EF hand (and vice versa). Indeed, extensive in ...
The ab initio method with NCSA and phase extension has been successfully implemented to determine the structure of the T = 3 GNNV icosahedral VLP. The key to success was the similarity of the mask (or the envelope) to the target structure. Despite significant variations in the main chains of the CP between FHV and GNNV, the envelopes of these T = 3 capsids are somewhat similar to each other, especially in the spatial position of the P-domain at the quasi-threefold axis. Considering that the P-domain of FHV is much smaller than that of GNNV, the radius of the mask was typically increased to 13 Å to cover the entire structure of GNNV. Other trials using the large spherical-shell mask, which was cut by the bisector planes between neighbouring virus particles, were not successful in phasing. On inspection of this spherical-shell mask, we found that it was so small, covering only half of the P-domain, as to result in a negative effect on the phasing. Tests investigating the simulation trials using ...
Plasmid mEmerald-Calnexin-N-14 from Dr. Michael Davidsons lab contains the insert Calnexin. This plasmid is available through Addgene.
RhoJ is a RhoGTPase expressed in endothelial cells and tumour cells which regulates cell motility, invasion, endothelial tube formation and focal adhesion numbers. This study aimed to further delineate the molecular function of RhoJ. Using timelapse microscopy RhoJ was found to regulate focal adhesion disassembly; siRNA-mediated knockdown of RhoJ increased focal adhesion disassembly time, while expression of an active mutant (daRhoJ) decreased it. Further, daRhoJ co-precipitated with the GIT-PIX complex, a regulator of focal adhesion disassembly. An interaction between daRhoJ and GIT1 was confirmed using yeast-2-hybrid, which depended on the Spa homology domain of GIT1. GIT1, GIT2, β-PIX and RhoJ all co-localised in focal adhesions and depended on each other for their recruitment to focal adhesions. Functionally, the GIT-PIX complex regulated endothelial tube formation, with knockdown of GIT1/2 or β-PIX phenocopying RhoJ knockdown. RhoJ knockout mice showed reduced tumour growth and diminished ...
Dermatophagoides farinae is an important source of indoor allergens that shows strong tolerance to external temperatures. However, the regularity and mechanism of tolerance are still unclear. Based on our previous RNA-seq and annotation of D. farinae under temperature stress, it is planned to identify differentially expressed genes (DEGs) involved in the temperature stress response by quantitative real-time PCR (qRT-PCR). However, the lack of reference genes directly limited the detection and confirmation of DEGs. Accordingly, in this study, we have selected six candidates as reference genes in D. farinae: 60S RP L11, 60S RP L21, α tubulin, GAPDH, Der f Mal f 6, and calreticulin, and evaluated their expression stabilities as affected by heat and cold stresses, using geNorm, NormFinder, BestKeeper, comparative ΔCt and RefFinder methods. Then the expression level of 15 DEGs were detected and verified. geNorm analysis showed that α tubulin and calreticulin were the most stable reference genes ...
We have identified novel interactions between ER chaperones and foldases using different methods tailored for the ER. The affinity capture and tagged bait experiments detect complexes whereas ER-MYTHS defines binary interactions. Using these methods, we have developed a high quality map that is rich in new interactions between ER lumenal proteins, and we have defined in detail one type of physical and functional interaction.. A remarkable finding was the interaction of six different PDI family members with PPIs. Interaction between PDIs and PPIs that catalyze rate-limiting steps of protein folding could allow their activities to be concentrated simultaneously on a folding substrate protein. Functional PDI-PPI interactions have been investigated in vitro (51, 52), with one study demonstrating that an interaction between bovine PDI and cyclophilin B modestly enhanced the chaperone activity of PDI (53). Although we observed no effect of cyclophilin B on the oxidoreductase activity of ERp72 in ...
Transporter associated with antigen processing (TAP) is a member of the ATP-binding-cassette transporter family. It delivers cytosolic peptides into the endoplasmic reticulum (ER), where they bind to nascent MHC class I molecules. The TAP structure is formed of two proteins: TAP-1 and TAP-2, which have one hydrophobic region and one ATP-binding region each. They assemble into a heterodimer, which results in a four-domain transporter. The TAP transporter is found in the ER lumen associated with the peptide-loading complex (PLC). This complex of β2 microglobulin, calreticulin, ERp57, TAP, tapasin, and MHC class I acts to keep hold of MHC molecules until they have been fully loaded with peptides. TAP-mediated peptide transport is a multistep process. The peptide-binding pocket is formed by TAP-1 and TAP-2. Association with TAP is an ATP-independent event, in a fast bimolecular association step, peptide binds to TAP, followed by a slow isomerisation of the TAP complex. It is suggested that the ...
Materials. Rat α2B-AR in vector pcDNA3, human β2-AR in vector pBC, rat AT1R in vector pCDM8 and human α1B-AR tagged with green fluorescent protein (GFP) at its C terminus were kindly provided by Drs. Stephen M. Lanier, Dr. John D. Hildebrandt (Medical University of South Carolina, Charleston, SC), Kenneth E. Bernstein, and Kenneth P. Minneman (Emory University, Atlanta, GA), respectively. Antibodies against GFP, phospho-ERK1/2, calnexin, and calreticulin were purchased from Santa Cruz Biotechnology, Inc. (Santa Cruz, CA). Anti-ERK antibodies detecting total ERK1/2 expression were from Cell Signaling Technology, Inc. (Danvers, MA). The α2-AR agonist UK14304, rauwolscine, dimethyl sulfoxide (DMSO), and protein G-Sepharose 4B were obtained from Sigma-Aldrich (St. Louis, MO). [3H]RX821002 (specific activity, 41 Ci/mmol), [3H]CGP12177 (51 Ci/mmol), [7-methoxy-3H]prazosin (70 Ci/mmol), and [125I-Sar1, Ile8]angiotensin II (125I-Ang II) (2200 Ci/mmol) were purchased from PerkinElmer Life and ...
To obtain valuable insights into the anti-inflammatory and anti-atherosclerosis mechanisms of melittin, two-dimensional (2-D) gel electrophoresis and MALDI-TOF/TOF were used. The proteome study, we showed 33 significant proteins that were differentially expressed in the cells treated with tumor necrosis factor alpha and melittin. Thirteen proteins were significantly increased in the cells treated with tumor necrosis factor alpha, and those proteins were reduced in the cells treated with melittin. Five of the proteins that showed increased expression in the cells treated with tumor necrosis factor alpha are involved in cell migration, including calreticulin, an essential factor of development that plays a role in transcription regulation. The proteins involved in cell migration were reduced in the melittin treated cells. The observed changes in the expression of GRP75, prohibitin, and a select group of other proteins were validated with reverse transcribed-PCR. It was confirmed that the observed ...
Buy our Recombinant Human Calnexin protein. Ab117167 is a protein fragment produced in Escherichia coli and has been validated in SDS-PAGE. Abcam provides free…
Obesity-mediated inflammation is a major cause of insulin resistance, and macrophages play an important role in this process. The 78-kDa glucose-regulated protein (GRP78) is a major endoplasmic reticulum chaperone that modulates unfolded protein response (UPR), and mice with GRP78 heterozygosity were resistant to diet-induced obesity. Here, we show that mice with macrophage-selective ablation of GRP78 (Lyz- GRP78(-/-)) are protected from skeletal muscle insulin resistance without changes in obesity compared with wild-type mice after 9 wk of high-fat diet. GRP78-deficient macrophages demonstrated adapted UPR with up-regulation of activating transcription factor (ATF)-4 and M2-polarization markers. Diet-induced adipose tissue inflammation was reduced, and bone marrow-derived macrophages from Lyz- GRP78(-/-) mice demonstrated a selective increase in IL-6 expression. Serum IL-13 levels were elevated by | 4-fold in Lyz- GRP78(-/-) mice, and IL-6 stimulated the myocyte expression of IL-13 and IL-13 receptor.
Shell formation and changes in body shape are important components of abalone development. The 2-DE results showed that at least two proteins (calmodulin (spot 75) [37] and calreticulin (spot 118) [38]) upregulated in the trochophore stage are involved in molluscan shell formation. Calmodulin and calreticulin were also identified in the larvae of the snail P. canaliculata during shell development [22] and in the Pacific oyster C. gigas [13]. The upregulation of both proteins indicates that they may contribute to the calcification of larval shells. According to the label-free analysis, additional proteins (CaM kinase II alpha, cadherin-like 3 protein, and calponin) involved in calcium ion transport and regulation were upregulated in the veliger stage. These proteins are likely involved in shell formation that occurs between trochophore and veliger larvae. In addition, calreticulin, as a protein-folding-related protein, can bind to misfolded proteins and either correct the protein folding or ...
My major interest is in antigen processing, defined as the combination of mechanisms that generate the complexes of class I and class II MHC molecules with peptides that are the targets for recognition by T lymphocytes. My colleagues and I have identified a number of proteins that collaborate in these processes. MHC class I peptide binding occurs in the context of a large complex that we have defined in the endoplasmic reticulum consisting of TAP, an ATP-dependent peptide transporter; tapasin, a protein that couples the transporter to assembling class I molecules; and two "house-keeping" chaperones, calreticulin and ERp57. How these accessory molecules combine to facilitate peptide binding is currently being intensively investigated. We have also studied MHC class II peptide binding through the mechanism of class II molecules being delivered into the endocytic pathway by an associated protein, the invariant chain. This has included study of the CLIP, a residual fragment of the invariant chain, ...
A total of 83 patients had TH or IMP for circulatory support; 20 patients had device implantation for RCS (12 TH and 8 IMP). Mean age was 54.1±16.4, 80% of patients were male, 45% smokers, 35% diabetic and 20% CRI. Ischemic cardiomyopathy was the etiology of RCS in 55% of patients. Ejection fraction averaged 21±12%. IMP patients were older (66±9 vs. 46±15, p=0.004). The overall mortality was 65% (TH 58.3% vs. IMP 75%, p=0.64). Table outlines in-hospital outcomes. ...
Baseline and procedural characteristics are described in the table below. Perforation occurred in 0.9% (n=1), dissection occurred in 1.8% (n=2), and no-reflow phenomenon occurred in 0.9% of cases (n=1). There were no cases of bleeding complications, emergent bypass, 30-day MI, 30-day TVR, or stent thrombosis. 1 (0.9%) patient had a stroke within 30 days of PCI. Restenosis occurred in 3.6% of patients (n=4). 30 day mortality occurred in 1.8% of patients (n=2) due to non-cardiac causes from post-operative complications from non-cardiac surgery. ...
In this thesis, the syntheses of oligosaccharides for interaction studies with various lectins are described. The first section reports the syntheses of tetra, tri- and disaccharides corresponding to truncated versions of the glucosylated arm of Glc1Man9(GlcNAc)2, found in the biosynthesis of N-glycans. The thermodynamic parameters of their interaction with calreticulin, a lectin assisting and promoting the correct folding of newly synthesised glycoproteins, were established by isothermal titration calorimetry. In the second section, a new synthetic pathway leading to the same tetra- and trisaccharides is discussed. Adoption of a convergent strategy and of a different protecting group pattern resulted in significantly increased yields of the target structures. The third section describes the syntheses of a number of monodeoxy-trisaccharides related to the above trisaccharide Glc-α-(1→3)-Man-α-(1→2)-Man-α-OMe. Differentsynthetic approaches were explored and the choice of early introduction ...
View mouse Tarbp2 Chr15:102518192-102523676 with: phenotypes, sequences, polymorphisms, proteins, references, function, expression
MGCKGDASGACAAGALPVTGVCYKMGVLVVLTVLWLFSSVKADSKAITTSLTTKWFSTPLLLEASEFLAE 1 - 70 DSQEKFWNFVEASQNIGSSDHDGTDYSYYHAILEAAFQFLSPLQQNLFKFCLSLRSYSATIQAFQQIAAD 71 - 140 EPPPEGCNSFFSVHGKKTCESDTLEALLLTASERPKPLLFKGDHRYPSSNPESPVVIFYSEIGSEEFSNF 141 - 210 HRQLISKSNAGKINYVFRHYIFNPRKEPVYLSGYGVELAIKSTEYKAKDDTQVKGTEVNTTVIGENDPID 211 - 280 EVQGFLFGKLRDLHPDLEGQLKELRKHLVESTNEMAPLKVWQLQDLSFQTAARILASPVELALVVMKDLS 281 - 350 QNFPTKARAITKTAVSSELRTEVEENQKYFKGTLGLQPGDSALFINGLHMDLDTQDIFSLFDVLRNEARV 351 - 420 MEGLHRLGIEGLSLHNVLKLNIQPSEADYAVDIRSPAISWVNNLEVDSRYNSWPSSLQELLRPTFPGVIR 421 - 490 QIRKNLHNMVFIVDPAHETTAELMNTAEMFLSNHIPLRIGFIFVVNDSEDVDGMQDAGVAVLRAYNYVAQ 491 - 560 EVDDYHAFQTLTHIYNKVRTGEKVKVEHVVSVLEKKYPYVEVNSILGIDSAYDRNRKEARGYYEQTGVGP 561 - 630 LPVVLFNGMPFEREQLDPDELETITMHKILETTTFFQRAVYLGELPHDQDVVEYIMNQPNVVPRINSRIL 631 - 700 TAERDYLDLTASNNFFVDDYARFTILDSQGKTAAVANSMNYLTKKGMSSKEIYDDSFIRPVTFWIVGDFD 701 - 770 SPSGRQLLYDAIKHQKSSNNVRISMINNPAKEISYENTQISRAIWAALQTQTSNAAKNFITKMAKEGAAE 771 - 840 ...
I love my new imac but i miss my crt it was perfect no matter what resolution it looked great now on the new imac i have to change the resolution...
Calreticulin (CRT) and citrullinated (citCRT) are implicated in rheumatoid arthritis (RA) pathology. citCRT binds to RA shared epitopes (SE) on HLA-DR molecules with high affinity and triggers pro-inflammatory events in adjacent cells. The aim of the study was to detect the presence of citCRT prior to developing RA and evaluate if citCT is a target for autoantibodies in RA cohorts with and without lung disease. Antibodies were assessed by ELISA against native CRT, citCRT and general protein citrullination, in sera from 50 RA patients without lung disease, 122 bronchiectasis (BR) patients, 52 bronchiectasis patients with RA (BRRA), 87 asthma patients and 77 healthy controls (HC). Serum citCRT was detected by immunoblotting and mass spectrometry. Genomic DNA was genotyped for HLA-DRB1 alleles. Patients were assessed for DAS28, rheumatoid factor, and anti-cyclic citrullinated peptide antibodies. Extracellular citCRT was detected in BR patients sera prior to them developing RA. A citCRT SE binding ...
Immunotherapeutic approaches to manage patients with advanced gastrointestinal malignancies are desired; however, mechanisms to incite tumor-specific immune responses remain to be elucidated. Rose bengal (RB) is toxic at low concentrations to malignant cells and may induce damage-associated molecular patterns; therefore, we investigated its potential as an immunomodulator in colon cancer. Murine and human colon cancer lines were treated with RB (10% in saline/PV-10) for cell cycle, cell death, and apoptosis assays. Damage-associated molecular patterns were assessed with western blot, ELISA, and flow cytometry. In an immunocompetent murine model of colon cancer, we demonstrate that tumors regress upon RB treatment, and that RB induces cell death in colon cancer cells through G2/M growth arrest and predominantly necrosis. RB-treated colon cancer cells expressed distinct hallmarks of immunogenic cell death (ICD), including enhanced expression of calreticulin and heat-shock protein 90 on the cell ...
Calreticulin (CRT) is a multifaceted protein, initially discovered as an endoplasmic reticulum (ER) chaperone protein, that is essential in calcium metabolism. Various implications in cancer, early development and immunology have been discovered more recently for CRT, as well as its role as a dominant eat-me prophagocytic signal. Intriguingly, cell-surface exposure/secretion of CRT is among the infective strategies used by parasites such as Trypanosoma cruzi, Entamoeba histolytica, Taenia solium, Leishmania donovani and Schistosoma mansoni. Because of the inherent flexibility of CRTs, their analysis by X-ray crystallography requires the design of recombinant constructs suitable for crystallization, and thus only the structures of two very similar mammalian CRT lectin domains are known. With the X-ray structures of two distant parasite CRTs, insights into species structural determinants that might be harnessed to fight against the parasites without affecting the functions of the host CRT are ...
Any of a group of proteins in living cells that assist newly synthesized or denatured proteins to fold into their functional three-dimensional structures. The chaperones bind to the protein and prevent improper interactions within the polypeptide chain, so that it assumes the correct folded orientation. This process may require energy in the form of ATP. Other functions include assisting the translocation of proteins across the membranes of cell organelles and binding denatured proteins under stress conditions or in degenerative disease. There are several unrelated families of chaperones, including five classes of heat-shock proteins - HSP25 (small heat-shock proteins), HSP60, HSP70, HSP90, and HSP100 - chaperonins, calnexin, and calreticulin. ...
Retro-translocation from the endoplasmic reticulum (ER) to the cytosol of secretory and membrane proteins takes place on misfolded molecules targeted for proteasomal degradation, in a process called ER associated degradation (ERAD), Because of the difficulties in clearly discriminating the fraction of molecules already retro-translocated from the ones in the ER, we took advantage of the E coli biotin-ligase (BirA) expressed in the cytosol of mammalian cells, to specifically biotin-label proteins that undergo retro-translocation, The method was validated using four different model proteins, known to undergo retro-translocation upon different conditions; the MHC-Iα chain, the non-secretory null-Hong Kong mutant of 01 antitrypsin, the immunoglobulin γH chain and calreticulin, The -- specific mono-biotinylation of only cytosolically dislocated molecules resulted in a novel quantitative method to determine the extent of retro-translocation. The method was used to study dislocation of CD4 and ...
Collectively, the studies discussed demonstrate that occasional patients with CALR mutation-positive essential thrombocythemia or myelofibrosis carry other myeloproliferative neoplasms-initiating genetic mutations (including JAK2 V617F), acquire "secondary mutations" before or after the CALR mutation, or evolve over time to being CALR mutation-homozygous.. Br J Haematol ...
Purpose: We previously revealed that the calreticulin (CRT) gene is a candidate oncogene promoting cell migration and invasion and that neuropilin-1 (NRP1) is a possible effector downstream of CRT in esophageal squamous carcinoma cells. This study aims to explore the mechanisms underlying the migration and invasion of esophageal cancer cells regulated by CRT through NRP1.. Experimental Design: Quantitative reverse-transcription polymerase chain reaction, Western blot analysis, chromatin immunoprecipitation, and reporter gene assays were used to investigate the relationship between CRT and NRP1. In vitro and in vivo assays were carried out to evaluate the effects of NRP1 on malignant phenotypes of ESCC cells and tumor metastasis in NOD/SCID mice. Immunohistochemistry was performed to analyze the expression of CRT and NRP1 in esophageal squamous cell carcinomas (ESCC).. Results: Knockdown of CRT decreased the expression of NRP1. Inhibition of NRP1 reduced ESCC cell motility in vitro and ...
Induction of apoptosis by nonsteroidal anti-inflammatory drugs, such as celecoxib, is involved in their antitumor activity. An endoplasmic reticulum chaperone, 150-kDa oxygen-regulated protein (ORP150) is essential for the maintenance of cellular viability under hypoxia and is reported to be overexpressed in clinically isolated tumors. We here found that ORP150 was up-regulated by celecoxib in human gastric carcinoma cells. In conjunction with the suppression of tumor growth, orally administered celecoxib up-regulated ORP150 in xenograft tumors. Both the ATF4 and ATF6 pathways were activated by celecoxib, and suppression of ATF4 and ATF6 mRNA expression by small interfering RNA (siRNA) inhibited the celecoxib-dependent up-regulation of ORP150. Celecoxib administration led to an increase in the intracellular concentration of Ca2+, whereas 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid-acetoxymethyl ester, an intracellular Ca2+ chelator, inhibited the up-regulation of ORP150 and the ...
BACKGROUND Hematopoietic malignancies are a group of blood cell disorders characterized by abnormal hematopoietic proliferation. OBJECTIVE The identification of specific clinicopathologic characteristics and tumor-related gene status provides critical information on potential therapeutic targets. METHODS The specimens were tested with immunohistochemistry, flow cytometry, RT-PCR and fragment analysis. RESULTS In this study, a patient with a long history of tobacco use was reported with a diagnosis of simultaneous low-grade B-cell lymphoproliferative disorder (LPD) and myeloproliferative neoplasm (MPN). Mutational analysis revealed that JAK2 V617F mutation and CALR mutation with 52bp deletion were present in this patient. CONCLUSION These results suggest that lymphoproliferative and myeloproliferative neoplasms may coexist, although the pathogenetic mechanism of coexisting hematologic requires further investigation. Additionally, the data indicate that JAK2 V617F and CALR mutations are not
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A friend asked me today what could be expected between a CRTs life and a LCDs life. His question came from two perspectives. His experience using CRTs and Flat
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References:. Mesa RA, Verstovsek S, Cervantes F, Barosi G, Reilly JT, Dupriez B, et al. Primary myelofibrosis (PMF), post polycythemia vera myelofibrosis (post-PV MF), post essential thrombocythemia myelofibrosis (post-ET MF), blast phase PMF (PMF-BP): Consensus on terminology by the international working group for myelofibrosis research and treatment (IWG-MRT). Leuk Res. 2007 Jun. 31(6):737-40.. Klampfl T, Gisslinger H, Harutyunyan AS, Nivarthi H, Rumi E, Milosevic JD, et al. Somatic mutations of calreticulin in myeloproliferative neoplasms. N Engl J Med. 2013 Dec 19. 369(25):2379-90.. Nangalia J, Massie CE, Baxter EJ, Nice FL, Gundem G, Wedge DC, et al. Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. N Engl J Med. 2013 Dec 19. 369(25):2391-405.. Verstovsek S, Mesa RA, Gotlib J, Levy RS, Gupta V, DiPersio JF, et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med. 2012 Mar 1. 366(9):799-807.. Gangat N, Caramazza D, Vaidya R, ...
In recent years, gold compounds have gained more and more attentions in the design of new metal anticancer drugs. Numerous researches have reported that gold compounds, in addition to their widely studied cytotoxic antitumor effects, also reverse tumor immune escape and directly facilitate the functions of immune cells, leading to enhanced anticancer effects. This review mainly summarizes our current understandings of antitumor effects of gold drugs and their relationships with various aspects of antitumor immunity, including innate immunity, adaptive immunity, immunogenic cell death, and immune checkpoints, as well as their roles in adverse effects. Some recent examples of anticancer gold compounds are highlighted. The property of gold compounds is expected to combine with anticancer immunotherapy, such as immune checkpoint inhibitors, to develop new anticancer therapeutic strategies.
Background: The discovery of somatic acquired mutations of JAK2 (V617F) in Philadelphia-negative myeloproliferative neoplasms (Ph-negative MPNs) including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) has not only improved rational disease classification and prognostication but also brings new understanding insight into the pathogenesis of diseases. Dosage effects of the JAK2 (V617F) allelic burden in Ph-negative MPNs may partially influence clinical presentation, disease progression, and treatment outcome. Material and Methods: Pyrosequencing was performed to detect JAK2 (V617F) and MPL (W515K/L) and capillary electrophoresis to identify CALR exon 9.0 mutations in 100.0 samples of Ph-negative MPNs (38.0 PV, 55 ET, 4 PMF, and 3 MPN-U). Results: The results showed somatic mutations of JAK2 (V617F) in 94.7% of PV, 74.5% of ET, 25.0% of PMF, and all MPN-U. A high proportion of JAK2 (V617F) mutant allele burden (mutational load | 50.0%) was predominantly observed
Being a major factory for protein synthesis, assembly, and export, the endoplasmic reticulum (ER) has a precise and robust ER quality control (ERQC) system monitoring its product line. However, when organisms are subjected to environmental stress, whether biotic or abiotic, the levels of misfolded proteins may overwhelm the ERQC system, tilting the balance between the capacity of and demand for ER quality control and resulting in a scenario termed ER stress. Intense or prolonged ER stress may cause damage to the ER as well as to other organelles, or even lead to cell death in extreme cases. To avoid such serious consequences, cells activate self-rescue programs to restore protein homeostasis in the ER, either through the enhancement of protein-folding and degradation competence or by alleviating the demands for such reactions. These are collectively called the unfolded protein response (UPR). Long investigated in mammalian cells and yeasts, the UPR is also of great interest to plant scientists. Among
The endoplasmic reticulum (ER) is an intracellular organelle for protein folding, lipid synthesis and Ca²⁺ storage. It is also responsible for the transportation for most of the secretory and transmembrane proteins. When the protein load exceeds the ER folding capacity, the ER undergoes stress and activates a set of signaling cascades that is termed the unfolded protein response (UPR). The multifunctional GRP78 is the major ER molecular chaperone with protein folding abilities and the master regulator of the UPR, and recently has been shown that a subfraction of it is localized on the cell surface acting as a co-receptor for various signaling pathway activation. ❧ Traditionally GRP78 is regarded as protective against hypoxia and nutrient starvation prevalent in the microenvironment of solid tumors, thus, its role in the development of hematologic malignancies remains to be determined. In this thesis, elevated GRP78 expression was detected in leukemic blasts of adult patients, leukemia cell ...
I am sure that this is advice given to many. Yet this is the first time I had heard it. One of my physical therapists, back in 2011, was intent on helping me walk straighter and I really tried and continue to try literally years after, yet I keep catching myself walking hunched over. When I see myself reflected I try to straighten myself out but clearly I needed another way to approach this. When Carmen said "lead with your hips" I knew she had given me a gift that might make a huge difference in my life ...
Somatic mutations of calreticulin in myeloproliferative neoplasms. N Engl J Med 2013;369:2379-2390 ...
"Protein acyltransferase function of purified calreticulin. Part 1: Characterization of propionylation of protein utilizing ...
ISBN 978-0-12-383863-6. Nash, Piers D.; Opas, Michal; Michalak, Marek (1994). "Calreticulin: Not just another calcium-binding ...
In 2013, two groups detected calreticulin mutations in a majority of JAK2-negative/MPL-negative patients with essential ... "Somatic mutations of calreticulin in myeloproliferative neoplasms". The New England Journal of Medicine. 369 (25): 2379-90. doi ...
Another externalized molecule marking apoptotic cells is calreticulin. Generally, the ability of apoptotic cells to change ... interacts with calreticulin which is a known C1q receptor), or complement receptors (CR3 and CR4). There is a variety of ... altered surface sugars on apoptotic cell and enable easier uptake by phagocytes which recognize their complex with calreticulin ...
July 1998). "Interaction between a Ca2+-binding protein calreticulin and perforin, a component of the cytotoxic T-cell granules ... 1998). "Interaction between a Ca2+-binding protein calreticulin and perforin, a component of the cytotoxic T-cell granules". ... Perforin has been shown to interact with calreticulin. Granzymes Defensin GRCh38: Ensembl release 89: ENSG00000180644 - Ensembl ...
He elucidated the molecular features of substrate recognition by endoplasmic reticulum chaperones calreticulin and Calnexin. He ... "Interactions of substrate with calreticulin, an endoplasmic reticulum chaperone". Journal of Biological Chemistry. 278 (8): ... "Isothermal titration calorimetric study defines the substrate binding residues of calreticulin". Biochemical and Biophysical ...
Calreticulin (CRT), one of the DAMP molecules, which is normally in the lumen of endoplasmic reticulum (ER), is translocated ... 2012). "A novel pathway combining calreticulin exposure and ATP secretion in immunogenic cancer cell death". EMBO J. 31 (5): ... "Calreticulin exposure dictates the immunogenicity of cancer cell death". Nature Medicine. 13 (1): 54-61. doi:10.1038/nm1523. ...
"Calreticulin exposure dictates the immunogenicity of cancer cell death". Nature Medicine. 13 (1): 54-61. doi:10.1038/nm1523. ...
... VIII and Calreticulin as Molecular Determinants of Sink Strength?". Plant Physiology. 126 (1): 39-46. doi:10.1104/pp. ...
After the β2-microglobulin binds to the MHC class I peptide-loading complex (PLC), calreticulin and ERp57 take over the job of ... Oliver JD, Hresko RC, Mueckler M, High S (Jun 1996). "The glut 1 glucose transporter interacts with calnexin and calreticulin ... Del Bem LE (Feb 2011). "The evolutionary history of calreticulin and calnexin genes in green plants". Genetica. 139 (2): 225-9 ... Otteken A, Moss B (Jan 1996). "Calreticulin interacts with newly synthesized human immunodeficiency virus type 1 envelope ...
Perrone L, Tell G, Di Lauro R (Feb 1999). "Calreticulin enhances the transcriptional activity of thyroid transcription factor-1 ... Perrone L, Tell G, Di Lauro R (Feb 1999). "Calreticulin enhances the transcriptional activity of thyroid transcription factor-1 ... NK2 homeobox 1 has been shown to interact with Calreticulin and PAX8. GRCh38: Ensembl release 89: ENSG00000136352 - Ensembl, ...
... cell surface calreticulin)". Immunopharmacology. 38 (1-2): 73-80. doi:10.1016/S0162-3109(97)00076-3. PMID 9476117. Karinch AM, ...
"Adiponectin modulates inflammatory reactions via calreticulin receptor-dependent clearance of early apoptotic bodies". J Clin ...
1994). "Calreticulin is released from activated neutrophils and binds to C1q and mannan-binding protein". Clin. Immunol. ... 1998). "The C1q and collectin binding site within C1q receptor (cell surface calreticulin)". Immunopharmacology. 38 (1-2): 73- ...
... and calreticulin". Immunity. 14 (3): 303-13. PMID 11290339. Williams SE, Inoue I, Tran H, Fry GL, Pladet MW, Iverius PH, ... "Low density lipoprotein receptor-related protein is a calreticulin coreceptor that signals focal adhesion disassembly". The ...
This protein of the endoplasmic reticulum interacts with lectin chaperones such as calreticulin and CNX in order to modulate ... This protein localizes to the endoplasmic reticulum (ER) and interacts with lectin chaperones calreticulin and calnexin (CNX) ... and polypeptide binding sites of calnexin and calreticulin". The Journal of Biological Chemistry. 277 (33): 29686-97. doi: ...
It was found that decreased CASQ2 is associated with high levels of calreticulin (CRT). In the absence of CASQ2 signal, CRT ... 2007). "Calsequestrin 2 (CASQ2) mutations increase expression of calreticulin and ryanodine receptors, causing ...
"Post-translational arginylation of calreticulin: a new isospecies of calreticulin component of stress granules". The Journal of ...
The peptide-loading complex consists of TAP, tapasin, MHC class I, calreticulin, and ERp57. Tapasin recruits MHC class I ... Sadasivan B, Lehner PJ, Ortmann B, Spies T, Cresswell P (August 1996). "Roles for calreticulin and a novel glycoprotein, ... "Roles for calreticulin and a novel glycoprotein, tapasin, in the interaction of MHC class I molecules with TAP". Immunity. 5 (2 ...
Lectin chaperones: calnexin and calreticulin Non-classical molecular chaperones: HSP47 and ERp29 Folding chaperones: Protein ... "TROSY-NMR reveals interaction between ERp57 and the tip of the calreticulin P-domain". Proc. Natl. Acad. Sci. U.S.A. 99 (4): ...
Calreticulin: Evidence has indicated the presence of the protein, calreticulin, within the cortical granule. Researchers have ... On the other hand, different research has shown that calreticulin may be released from vesicles other than cortical granules. ... Furthermore, upon exocytosis, this calreticulin interacts with the oocyte's cytoskeleton, thereby allowing the transmission of ... Additionally contributing to polyspermy prevention, calreticulin may also inhibit certain glycoproteins, which promote ...
Cunningham TJ, Jing H, Wang Y, Hodge L (2000). "Calreticulin binding and other biological activities of survival peptide Y-P30 ...
The network of endoplasmic reticulum-resident chaperones (ERp72, GRP94, calreticulin, and BiP) interacts with apolipoprotein b ... calreticulin, and cyclophilin B". The Journal of Biological Chemistry. 278 (9): 7459-68. doi:10.1074/jbc.M207976200. PMID ... "C1q and mannose binding lectin engagement of cell surface calreticulin and CD91 initiates macropinocytosis and uptake of ... "Low density lipoprotein receptor-related protein is a calreticulin coreceptor that signals focal adhesion disassembly". The ...
Calreticulin (CAL), which is known to bind calcium in most eukaryotic cells, is able to specifically bind to the first stem ... Pfam PF00262 - Calreticulin protein family Page for Rubella virus 3' cis-acting element at Rfam. ...
Calreticulin is also found in the nucleus, suggesting that it may have a role in transcription regulation. Calreticulin binds ... The term "Mobilferrin" is considered to be the same as calreticulin by some sources. Calreticulin binds to misfolded proteins ... Systemic lupus erythematosus is associated with increased autoantibody titers against calreticulin, but calreticulin is not a ... "Entrez Gene: CALR calreticulin". Nangalia J, Massie CE, Baxter EJ, Nice FL, Gundem G, Wedge DC, Avezov E, Li J, Kollmann K, ...
... Paul Eggleton eggleton at bioch.ox.ac.uk Thu Jun 17 11:21:46 EST 1999 *Previous message: Cb-Amp ... Dear All Please read attached document for details of 4th international CALRETICULIN workshop to be held at Oxford University ...
If you know of any papers that use this antibody, please contact us at antibodies [at] alzforum [dot] org for consideration in the References section.. ...
... Frank C Hay frank at rabbits.demon.co.uk Wed May 3 06:49:58 EST 1995 *Previous message: The Case of ... Does anyone have an antibody to human calreticulin that they can let us have for work on rheumatoid arthritis? Thanks Frank -- ...
This family includes Calreticulin, Calnexin and Camlegin. Michalak M, Milner RE, Burns K, Opas M (August 1992). "Calreticulin ... In molecular biology, the calreticulin protein family is a family of calcium-binding proteins. ...
Ecto-calreticulin in immunogenic chemotherapy.. Obeid M1, Tesniere A, Panaretakis T, Tufi R, Joza N, van Endert P, Ghiringhelli ... We discovered that the pre-apoptotic translocation of intracellular calreticulin (endo-CRT) to the plasma membrane surface ( ...
The discovery of mutations in exon 9 of the calreticulin (CALR) gene in the majority of cases of JAK2 wild-type essential ... Mutation of the Calreticulin (CALR) Gene in Myeloproliferative Neoplasms. Jason Gotlib, MD, MS Professor of Medicine Stanford ... Calreticulin mutation does not modify the IPSET score for predicting the risk of thrombosis among 1150 patients with essential ... The discovery of mutations in exon 9 of the calreticulin (CALR) gene in the majority of cases of JAK2 wild-type essential ...
Chicken polyclonal Calreticulin antibody validated for WB, IP, ICC, ICC/IF and tested in Human, Mouse, Rat and Rabbit. ... Western blot of calreticulin on HeLa cell extract using ab2908. Western blot of calreticulin on HeLa cell extract using ab2908. ... All lanes : Anti-Calreticulin antibody (ab2908) at 1/2000 dilution. Lane 1 : MCF7. Lane 2 : MDA-MB-231. Lane 3 : HeLa. Lane 4 ... Synthetic peptide corresponding to Mouse Calreticulin aa 399-414.. Sequence: DEKEEDEEESPGQAKD (Peptide available as ab4927). ...
PS00803. CALRETICULIN_1. 1 hit. PS00804. CALRETICULIN_2. 1 hit. PS00805. CALRETICULIN_REPEAT. 1 hit. ... PS00803. CALRETICULIN_1. 1 hit. PS00804. CALRETICULIN_2. 1 hit. PS00805. CALRETICULIN_REPEAT. 1 hit. ... IPR009169. Calreticulin. IPR009033. Calreticulin/calnexin_P_dom_sf. IPR013320. ConA-like_dom_sf. ... IPR009169. Calreticulin. IPR009033. Calreticulin/calnexin_P_dom_sf. IPR013320. ConA-like_dom_sf. ...
Buy our Recombinant Human Calreticulin protein. Ab40609 is a protein fragment produced in Escherichia coli and has been ... Recombinant Human Calreticulin protein images. * SDS-PAGE - Calreticulin protein (His tag) (ab40609) ... Calreticulin is also found in the nucleus, suggesting that it may have a role in transcription regulation. Calreticulin binds ... Systemic lupus erythematosus is associated with increased autoantibody titers against calreticulin but calreticulin is not a Ro ...
Abcam provides specific protocols for Anti-Calreticulin antibody (ab4109) : Western blot protocols, Immunohistochemistry ...
... via the calreticulin/calnexin cycle. This lectin interacts transiently with almost all of the monoglucosylated glycoproteins ... PS00803 CALRETICULIN_1, 1 hit. PS00804 CALRETICULIN_2, 1 hit. PS00805 CALRETICULIN_REPEAT, 3 hits. PS00014 ER_TARGET, 1 hit ... PS00803 CALRETICULIN_1, 1 hit. PS00804 CALRETICULIN_2, 1 hit. PS00805 CALRETICULIN_REPEAT, 3 hits. PS00014 ER_TARGET, 1 hit ... IPR009169 Calreticulin. IPR009033 Calreticulin/calnexin_P_dom_sf. IPR013320 ConA-like_dom_sf. ...
Rabbit recombinant monoclonal Calreticulin antibody [EPR3924] - ER Marker conjugated to PE. Validated in Flow Cyt, ICC/IF and ... Anti-Calreticulin antibody [EPR3924] - Low endotoxin, Azide free (ab211962) *Anti-Calreticulin antibody [EPR3924] - ER Marker ( ... Anti-Calreticulin antibody [EPR3924] - ER Marker (HRP) (ab195511) *Anti-Calreticulin antibody [EPR3924] - ER Marker (Alexa ... Anti-Calreticulin antibody [EPR3924] - ER Marker (Alexa Fluor® 647) (ab196159) *Anti-Calreticulin antibody [EPR3924] - ER ...
Calreticulin Polyclonal Antibody from Invitrogen for Western Blot, Immunofluorescence, Immunocytochemistry and ... Cite Calreticulin Polyclonal Antibody. The following antibody was used in this experiment: Calreticulin Polyclonal Antibody ... PA1-903 detects calreticulin from human, rat, mouse, hamster, rabbit and canine tissues.. PA1-903 has been successfully used in ... Calr or Calreticulin is a calcium-binding chaperone that promotes folding, oligomeric assembly and quality control in the ...
Calreticulin has also been suggested to be a component of the peptide loading complex where it interacts with other ER resident ... 9.0 9.1 Michalak, M., Groenendyk, J., Szabo, E., Gold, L. I. and Opas, M. Calreticulin, a multi-process calcium-buffering ... For a complete list of CFG data and resources relating to this paradigm, see the CFG database search results for calreticulin. ... 1.0 1.1 Ellgaard, L. and Frickel, E. M. Calnexin, calreticulin, and ERp57: teammates in glycoprotein folding. Cell Biochem ...
The exposure of calreticulin (CRT) on the plasma membrane can precede anthracycline-induced apoptosis and is required for cell ... The co-translocation of ERp57 and calreticulin determines the immunogenicity of cell death. *T Panaretakis1,2,3. na1, ... Calreticulin couples calcium release and calcium influx in integrin-mediated calcium signaling. Mol Biol Cell 2000; 11: 1433- ... Ecto-Calreticulin is essential for an efficient immunogenic cell death stimulation in mouse melanoma *Paola Giglio ...
Michael Davidsons lab contains the insert Calreticulin. This plasmid is available through Addgene. ... mEmerald-Calreticulin-N-16 was a gift from Michael Davidson (Addgene plasmid # 54023 ; http://n2t.net/addgene:54023 ; RRID: ...
Identification of calreticulin as a nuclear matrix protein associated with human colon cancer.. Brünagel G1, Shah U, Schoen RE ... The aim of this study was to confirm the identity of the protein as calreticulin as well as to evaluate the localization of ... The multi-functional protein, calreticulin, is normally found in the lumen of the endoplasmic reticulum although some reports ... The amino acid composition of this protein revealed sequence similarity with calreticulin. ...
These studies suggest that (a) calreticulin is regulated at the transcriptional level, and (b) calreticulin, like some other LE ... we have begun to examine the transcriptional regulation of calreticulin. A 504 bp calreticulin promoter fragment was subcloned ... Calreticulin is transcriptionally upregulated by heat shock, calcium and heavy metals.. Nguyen TO1, Capra JD, Sontheimer RD. ... Calreticulin is a new human rheumatic disease-associated autoantigen that plays a multifaceted role in cell biology. In earlier ...
Browse our Calreticulin-2/CALR3 Lysate catalog backed by our Guarantee+. ... Calreticulin-2/CALR3 lysate, CALR3 lysate, calreticulin 2 lysate, calreticulin 3 lysate, Calreticulin-2 lysate, calreticulin-3 ... Calreticulin-2/CALR3 Lysates. We offer Calreticulin-2/CALR3 Lysates for use in common research applications: Western Blot. Each ... Our Calreticulin-2/CALR3 Lysates can be used in a variety of model species: Human. Use the list below to choose the ...
Calreticulin, a multi-process calcium-buffering chaperone of the endoplasmic reticulum. Biochem J 2009;417(3):651-666. ... Mutations in the calreticulin gene (CALR) represented by deletions and insertions in exon 9 inducing a −1/+2 frameshift are ... Somatic mutations of calreticulin in myeloproliferative neoplasms. N Engl J Med 2013;369(25):2379-2390. ... Calreticulin is essential for cardiac development. J Cell Biol 1999;144(5):857-868. ...
In addition calreticulin is a major storage form for CALCIUM and functions as a calcium-signaling molecule that can regulate ... Calreticulin: A multifunctional protein that is found primarily within membrane-bound organelles. In the ENDOPLASMIC RETICULUM ... Calreticulin. Subscribe to New Research on Calreticulin A multifunctional protein that is found primarily within membrane-bound ... In addition calreticulin is a major storage form for CALCIUM and functions as a calcium-signaling molecule that can regulate ...
Calreticulin and calnexin are Ca2+-binding chaperones localized in the endoplasmic reticulum of eukaryotes acting in ... Calreticulin Calnexin Chaperones Evolution Green plants Electronic supplementary material. The online version of this article ( ... Crofts AJ, Denecke J (1998) Calreticulin and calnexin in plants. Trends Plants Sci 3:396-399CrossRefGoogle Scholar ... Calreticulin and calnexin possibly share a common origin, and both proteins are present along all green plants lineages. The ...
Order monoclonal and polyclonal Calreticulin antibodies for many applications. Selected quality suppliers for anti-Calreticulin ... Calreticulin (CALR) Antigen Profile Protein Summary Calreticulin is a multifunctional protein that acts as a major Ca(2+)- ... Calreticulin in Retinoic Acid Receptor Signaling Pathway * Calreticulin in Retinoic Acid Receptor Signaling Pathway ... Calreticulin in Intracellular Steroid Hormone Receptor Signaling Pathway * Calreticulin in Regulation of Intracellular Steroid ...
... but calreticulin is not a Ro/SS-A antigen. Earlier papers referred to calreticulin as an Ro/SS-A antigen, but this was later ... Functional analysis of recombinant calreticulin fragment 39-272: implications for immunobiological activities of calreticulin ... Calreticulin binds to the [[synthetic peptide]] KLGFFKR, which is almost identical to an amino acid sequence in the [[DNA- ... Transcription regulation === Calreticulin is also found in the nucleus, suggesting that it may have a role in transcription ...
  • We have also shown that high amounts of wild-type tapasin are still unable to associate with MHC class I in the absence of the MHC class I/calreticulin interaction, confirming the central role of calreticulin in the formation of the MHC class I assembly complex. (lu.se)
  • To date no information is available about the role of calreticulin in EGFR expression and folding. (qscience.com)
  • We discovered that the pre-apoptotic translocation of intracellular calreticulin (endo-CRT) to the plasma membrane surface (ecto-CRT) is critical for the recognition and engulfment of dying tumor cells by dendritic cells. (nih.gov)
  • 1 Recently, we reported that tumor cells undergoing immunogenic cell death translocate intracellular calreticulin (endo-CRT) to their plasma membrane (PM) surface (ecto-CRT), facilitating tumor cell recognition and engulfment by dendritic cells (DC) and subsequent T-cell-mediated elimination of the tumor. (nature.com)
  • In addition calreticulin is a major storage form for CALCIUM and functions as a calcium-signaling molecule that can regulate intracellular calcium HOMEOSTASIS. (curehunter.com)
  • Perturbation of intracellular Ca 2+ levels by prolonged exposure to either thapsigargin or ionomycin induced calreticulin mRNA, both in the presence and absence of extracellular Ca 2+ , consistent with the proposal that sustained depletion of the ER Ca 2+ store can trigger these increases. (biochemj.org)
  • A molecularly tagged form of calreticulin (CR), a low affinity-high capacity Ca2+ binding protein that resides in the ER lumen, was transiently transfected into HeLa cells to specifically modify the Ca2+ buffering capacity of the intracellular Ca2+ stores. (rupress.org)
  • Transactivation of the calreticulin promoter was also increased by fourfold in NIH/3T3 cells treated with bradykinin, a hormone that induces Ca 2+ release from the intracellular Ca 2+ stores. (elsevier.com)
  • These studies suggest that stress response to the depletion of intracellular Ca 2+ stores induces expression of the calreticulin gene in vitro and in vivo. (elsevier.com)
  • Next we will examine whether changes in the EGFR is due to calreticulin's role as a regulator of intracellular calcium thus affecting transcription of EGFR (using quantitative RT-PCR technique). (qscience.com)
  • The work demonstrates that mutated calreticulins hijack intracellular processing and the traffic to the cell surface of one key protein named thrombopoietin receptor (TpoR). (welbio.org)
  • We discuss the intriguing observations that the most abundant endoplasmic reticulum protein, calreticulin, the most abundant intracellular metabolite, ATP, and the most abundant non-histone chromatin-binding protein, HMGB1, can determine whether cell death is immunogenic as they appear on the surface or in the microenvironment of dying cells. (springer.com)
  • One of the features of an apoptotic cell is the presentation of a variety of intracellular molecules on the cell surface, such as calreticulin, phosphatidylserine (from the inner layer of the plasma membrane), annexin A1, oxidised LDL and altered glycans. (wikipedia.org)
  • Systemic lupus erythematosus is associated with increased autoantibody titers against calreticulin, but calreticulin is not a Ro/SS-A antigen. (wikipedia.org)
  • Earlier papers referred to calreticulin as an Ro/SS-A antigen, but this was later disproven. (wikipedia.org)
  • In vitro interaction of a polypeptide homologous to human Ro/SS-A antigen (calreticulin) with a highly conserved amino acid sequence in the cytopla. (nih.gov)
  • We demonstrate that Tc45, a polypeptide described as an immunogenetically restricted Trypanosoma cruzi antigen in mice, is calreticulin, a dimorphic molecule encoded by genes with variable chromosomal distribution. (ajtmh.org)
  • Calreticulin acts as an adjuvant to promote dendritic cell maturation and enhances antigen-specific cytotoxic T lymphocyte responses against non-small cell lung cancer cells. (semanticscholar.org)
  • Van Endert, Peter M. / Calreticulin promotes folding of functional human leukocyte antigen class I molecules in vitro . (elsevier.com)
  • Our data show that calreticulin can bind weakly to L-d without tapasin's assistance, and that deglycosylation of the alpha1 domain results in a primary loss of binding to calreticulin rather than tapasin. (lu.se)
  • Tapasin and calreticulin are essential for efficient MHC class I assembly, but their precise action during class I assembly remains to be elucidated. (elsevier.com)
  • Tc45, a dimorphic Trypanosoma cruzi immunogen with variable chromosomal localization, is calreticulin. (ajtmh.org)
  • In addition, evidence is provided to support a role for cell surface calreticulin (CRT) in (also known as the cC1qR) binding the collagenous tails of C1q and MBL attached to the apoptotic cell. (rupress.org)
  • Thrombospondin (TSP) signals focal adhesion disassembly (the intermediate adhesive state) through interactions with cell surface calreticulin (CRT). (rupress.org)
  • The amino terminus of calreticulin interacts with the DNA-binding domain of the glucocorticoid receptor and prevents the receptor from binding to its specific glucocorticoid response element. (wikipedia.org)
  • Using mutation studies we have concluded that overlapping as well as specific functions also could be assigned to the respective calreticulin isoforms. (lu.se)
  • In essential thrombocythemia, 154 (53%) Janus kinase 2 V617F, 96 (33%) calreticulin, 9 (3%) myeloproliferative leukemia virus oncogene gene mutation-positive and 30 triple-negative (11%) cases were identified, while in primary myelofibrosis 56 (57%) Janus kinase 2 V617F, 25 (25%) calreticulin, 7 (7%) myeloproliferative leukemia virus oncogene gene mutation-positive and 11 (11%) triple-negative cases were identified. (cdc.gov)
  • Patients positive for the calreticulin mutation were younger and had higher platelet counts compared to Janus kinase 2 mutation-positive counterparts. (cdc.gov)
  • Calreticulin mutation-positive patients with essential thrombocythemia showed a lower risk of developing venous thrombosis, but no difference in overall survival. (cdc.gov)
  • Calreticulin mutation-positive patients with primary myelofibrosis had a better overall survival compared to that of the Janus kinase 2 mutation-positive (P=0.04) or triple-negative cases (P=0.01). (cdc.gov)
  • Type 2 calreticulin mutation occurred more frequently in essential thrombocythemia than in primary myelofibrosis (P=0.049). (cdc.gov)
  • We confirm that calreticulin mutation is associated with distinct clinical characteristics and explored relationships between mutation type, load and clinical outcome. (cdc.gov)
  • Activation of the thrombopoietin receptor requires the glycan binding site and a novel C-terminal tail of the mutant calreticulin. (bloodjournal.org)
  • Baluska F, Samaj J, Napier R, Volkmann D (1999) Maize calreticulin localizes preferentially to plasmodesmata in root apex. (springer.com)
  • The molecular basis of this phenomenon remained basically unknown until our proposal that T. cruzi Calreticulin (TcCRT), an endoplasmic reticulum-resident chaperone, translocated-externalized by the parasite, may mediate at least an important part of this effect. (biomedcentral.com)
  • The purified recombinant NH 2 -terminal domain of calreticulin (amino acids 1-180) inhibited the proliferation of endothelial cells, but not cells of other lineages, and suppressed angiogenesis in vivo. (rupress.org)
  • This study evaluated the effect of a novel endogenous inhibitor of angiogenesis, calreticulin anti-angiogenic domain (CAD), subconjunctivally delivered by an adenoviral vector (Ad-CAD) in a rat model of laser-induced CNV. (edu.au)
  • Calreticulin can inhibit the binding of androgen receptor to its hormone-responsive DNA element and can inhibit androgen receptor and retinoic acid receptor transcriptional activities in vivo, as well as retinoic acid-induced neuronal differentiation. (wikipedia.org)
  • We demonstrate here that calreticulin acts as a second general recognition ligand by binding and activating LDL-receptor-related protein (LRP) on the engulfing cell. (diva-portal.org)
  • The endoplasmatic protein calreticulin (CRT), in conjunction with Low density lipoprotein Receptorrelated Protein 1 (LRP1) on the phagocyte, can act as a receptor for collectin family members and mediate uptake of apoptotic cells. (diva-portal.org)
  • Our results indicate that calreticulin may play a role in folding of the bradykinin receptor, which affects its ability to initiate InsP3-dependent Ca2+ release in calreticulin-deficient cells. (nih.gov)
  • We have shown that expression of the InsP3R is reduced in calreticulin-deficient (K42) cells, whereas expression of the bradykinin receptor is not. (nih.gov)
  • Altered calreticulin expression does not affect EGFR receptor folding but rather increases its expression and function. (qscience.com)
  • Thrombopoietin receptor MPL is required for calreticulin mutants to induce an essential thrombocythemia phenotype in transplanted mice. (osvilt.com)
  • This suggests that there are probably different mechanisms by which calreticulin expression can be induced in response to agents that affect normal ER functioning. (biochemj.org)
  • Nascent lipidated apolipoprotein B is transported to the Golgi as an incompletely folded intermediate as probed by its association with network of endoplasmic reticulum molecular chaperones, GRP94, ERp72, BiP, calreticulin, and cyclophilin B". The Journal of Biological Chemistry. (wikipedia.org)
  • Studies on transgenic mice reveal that calreticulin is a cardiac embryonic gene that is essential during development. (wikipedia.org)
  • A transgenic mouse whose genome comprises a transcriptional control region operably linked to a cDNA encoding calreticulin (CRT) is described. (justia.com)
  • Calreticulin binds to the synthetic peptide KLGFFKR, which is almost identical to an amino acid sequence in the DNA-binding domain of the superfamily of nuclear receptors. (wikipedia.org)
  • Can be blocked with Calreticulin peptide (ab4927) . (abcam.com)
  • Calreticulin displays in vivo peptide-binding activity and can elicit CTL responses against bound peptides. (semanticscholar.org)
  • We used a soluble single chain HLA-A2/β 2 - microglobulin molecule, A2SC, to study the effect of calreticulin on the peptide binding capacity of HLA class I molecules. (elsevier.com)
  • Calreticulin dramatically enhanced acquisition of peptide binding capacity when added to denatured A2SC molecules during refolding at 4 °C. However, it had no effect on the rapid loss of A2SC peptide binding capacity at physiological temperature. (elsevier.com)
  • We conclude that calreticulin promotes the folding of HLA class I molecules to a state in which, at low temperature, they spontaneously acquire peptide binding capacity. (elsevier.com)
  • Following full assembly, the glycan is transferred en bloc by the glycosyltransferase oligosaccharyltransferase to a nascent peptide chain, within the reticular lumen. (wikipedia.org)
  • Since modulation of the Ro/SS-A autoantigen in epidermal keratinocytes has been implicated in the pathogenesis of subacute cutaneous lupus erythematosus and neonatal lupus erythematosus, we have begun to examine the transcriptional regulation of calreticulin. (nih.gov)
  • Calcium ionophore, heat shock, and heavy metals such as zinc and cadmium were consistently found to increase calreticulin transcriptional activities in A431 cells (a human epidermoid squamous carcinoma cell line) under transient transfection conditions. (nih.gov)
  • These studies suggest that (a) calreticulin is regulated at the transcriptional level, and (b) calreticulin, like some other LE-related autoantigens, appears to function as a heat shock/stress-response gene. (nih.gov)
  • The mechanism underlying the induction seems to be transcriptional up-regulation as both agents increased calreticulin promoter-driven firefly luciferase expression in transfected cells to the same degree as the observed increases in calreticulin mRNA. (biochemj.org)
  • Thus either additional cis sequences that reside outside our promoter region are necessary for transcriptional activation by tunicamycin, or the increases in calreticulin mRNA occur post-transcriptionally. (biochemj.org)
  • The amino acid composition of this protein revealed sequence similarity with calreticulin. (nih.gov)
  • The NH2-terminal amino acid sequence of the polypeptide was found to be identical to calreticulin. (unige.ch)
  • To elucidate the function of CRTs in plant responses against drought, a main abiotic stress limiting cereal crop production worldwide, a full-length cDNA encoding calreticulin protein namely TaCRT was isolated from wheat ( Triticum aestivum L.). The deduced amino acid sequence of TaCRT shares high homology with other plant CRTs. (oup.com)
  • Ingestion of the apoptotic cells through calreticulin/CD91 stimulation is further shown to involve the process of macropinocytosis, implicated as a primitive and relatively nonselective uptake mechanism for C1q- and MBL-enhanced engulfment of whole, intact apoptotic cells, as well as cell debris and foreign organisms to which these molecules may bind. (rupress.org)
  • Another externalized molecule marking apoptotic cells is calreticulin. (wikipedia.org)
  • To distinguish them from living cells, apoptotic cells carry specific 'eat me' signals, such as the presence of phosphatidyl serine (resulting from phospholipid flip-flop) or calreticulin on the outer leaflet of the cell membrane. (wikipedia.org)
  • We have recently identified ( a ) ectocalreticulin as the main source of immunogenicity of cancer cell death induced by chemotherapy or radiotherapy, ( b ) ectoERP57 as critical protein for inducing cell surface exposure of calreticulin, and ( c ) that ectoERP57 and ectocalreticulin are cotranslocated together to the tumor cell surface by the mediator of the inhibition of PP1/GADD34 complex. (aacrjournals.org)
  • Similarly, lung tumor cell lines isolated from calreticulin over expressing cells expressed high levels of EGFR. (qscience.com)
  • Phylogenetic analyses and expression profiling revealed that both monocotyledons and eudicotyledons contain two distinct calreticulin isoform groups: a Crt1/Crt2 and a Crt3 group. (lu.se)
  • Increased CD47 expression correlated with high amounts of calreticulin on cancer cells and was necessary for protection from calreticulin-mediated phagocytosis. (sciencemag.org)
  • Furthermore, increased calreticulin expression was an adverse prognostic factor in diverse tumors including neuroblastoma, bladder cancer, and non-Hodgkin's lymphoma. (sciencemag.org)
  • Calreticulin-induced phagocytosis of cancer cells can be counterbalanced by CD47 expression. (sciencemag.org)
  • Baksh S, Michalak M (1991) Expression of calreticulin in Escherichia coli and identification of its Ca 2+ binding domains. (springer.com)
  • To determine whether intra-uterine growth retardation or programmed hypertension was associated with altered calreticulin or calsequestrin expression, effects of prenatal glucocorticoid overexposure (maternal dexamethasone treatment on days 15-21 of pregnancy) were examined during fetal life and postnatal development until adulthood (24 weeks). (biochemj.org)
  • In control offspring, cardiac calreticulin protein expression declined between 2 and 3 weeks of age, and remained suppressed until adulthood. (biochemj.org)
  • We have investigated whether agents that affect these processes can alter calreticulin expression in HeLa cells. (biochemj.org)
  • Molecular characteristics and expression analysis of calreticulin in Chinese shrimp Fenneropenaeus chinensis. (semanticscholar.org)
  • Bradykinin binding and bradykinin-induced Ca2+ release are both restored by expression of full-length calreticulin and the N + P domain of the protein. (nih.gov)
  • Expression of the P + C domain of calreticulin does not affect bradykinin-induced Ca2+ release but restores the ER Ca2+ storage capacity. (nih.gov)
  • Coexpression analyses indicated several components with similar expression patterns as the respective calreticulins, suggesting that they might be part of the same functional units in the cell. (lu.se)
  • Changes in the concentration of extracellular and cytoplasmic Ca 2+ did not affect the increased expression of the calreticulin gene. (elsevier.com)
  • We have named this NH 2 -terminal domain of calreticulin vasostatin. (rupress.org)
  • We concluded that the C domain of calreticulin plays a role in Ca2+ storage and that the N domain may participate in its chaperone functions. (nih.gov)
  • The exposure of calreticulin (CRT) on the plasma membrane can precede anthracycline-induced apoptosis and is required for cell death to be perceived as immunogenic. (nature.com)
  • 1) Kageyama S, et al : Identification by Proteomic Analysis of Calreticulin as a Marker for Bladder Cancer and Evaluation of the Diagnostic Accuracy of Its Detection in Urine. (cosmobio.com)
  • Calreticulin also participates in the reactions yielding assembly of peptides onto nascent MHC class I molecules. (semanticscholar.org)