Journal ArticleBiomedicines · May 24, 2022
The 78 kDa glucose-regulated protein (GRP78), a member of the 70 kDa heat-shock family of molecular chaperones (HSP70), is essential for the regulation of the unfolded protein response (UPR) resulting from cellular endoplasmic reticulum (ER) stress. During ...
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Journal ArticleIUBMB life · June 2021
The 78 kDa glucose-regulated protein (GRP78) is an endoplasmic reticulum (ER)-resident molecular chaperone. GRP78 is a member of the 70 kDa heat shock family of proteins involved in correcting and clearing misfolded proteins in the ER. In response to cellu ...
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Chapter · January 1, 2018
The plasminogen (Pg) activator system plays an important role in the central nervous system (CNS), including processes of neuronal migration, neurite outgrowth, and neuronal plasticity. Pg and tissue-type plasminogen activator (t-PA) are primarily involved ...
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Journal ArticleJ Biol Chem · December 22, 2017
Tumor cells display on their surface several molecular chaperones that normally reside in the endoplasmic reticulum. Because this display is unique to cancer cells, these chaperones are attractive targets for drug development. Previous epitope-mapping of a ...
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Journal ArticleBiochem Biophys Res Commun · August 26, 2017
Myelin basic protein (MBP) is a key component of myelin, the specialized lipid membrane that encases the axons of all neurons. Both plasminogen (Pg) and tissue-type plasminogen activator (t-PA) bind to MBP with high affinity. We investigated the kinetics a ...
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Journal ArticleJ Biol Chem · May 13, 2016
Activated α2-macroglobulin (α2M*) signals predominantly through cell surface GRP78 (CS-GRP78) to promote proliferation and survival of cancer cells; however, the molecular mechanism remains obscure. c-MYC is an essential transcriptional regulator that cont ...
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Journal ArticleSemin Ophthalmol · 2016
PURPOSE: To report a novel plasminogen gene mutation and detection of anti-plasminogen antibodies in a patient with ligneous conjunctivitis successfully treated with 60% fresh frozen plasma (FFP). METHODS: Retrospective data collected on a 45-year-old Cauc ...
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Journal ArticleJ Neuroimmunol · October 15, 2015
Autoantibodies from autistic spectrum disorder (ASD) patients react with multiple proteins expressed in the brain. One such autoantibody targets myelin basic protein (MBP). ASD patients have autoantibodies to MBP of both the IgG and IgA classes in high tit ...
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Journal ArticleJ Biol Chem · September 5, 2014
The glucose-regulated protein 78 (GRP78) is a plasminogen (Pg) receptor on the cell surface. In this study, we demonstrate that GRP78 also binds the tissue-type plasminogen activator (t-PA), which results in a decrease in K(m) and an increase in the V(max) ...
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Journal ArticleJ Biol Chem · January 4, 2013
The voltage-dependent anion channel (VDAC), a major pore-forming protein in the outer membrane of mitochondria, is also found in the plasma membrane of a large number of cells where in addition to its role in regulating cellular ATP release and volume cont ...
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Journal ArticleMelanoma Res · August 2011
A correlation between expression of the glucose-regulated protein of 78 kDa (GRP78) in malignant melanoma tumors and poor patient survival is well established. In this study, in addition to demonstrating the expression of GRP78 in tumor tissue, we investig ...
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Journal ArticleMelanoma Res · February 2011
Autoantibodies that react with GRP78 expressed on the cell-surface of many tumor cell lines occur in the sera of patients with prostate cancer, melanoma, and ovarian cancer. These autoantibodies are a negative prognostic factor in prostate cancer and, when ...
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Journal ArticleJ Neuroimmunol · October 8, 2010
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Autistic children show elevated serum levels of autoantibodies to several proteins essential for the function of normal brains. The voltage-dependent anion channel (VDAC) and hexokinase-I, a VDAC protective ligand, were identified as targets of this autoim ...
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Journal ArticleJ Biol Chem · September 10, 2010
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The increased risk of venous thromboembolism in cancer patients has been attributed to enhanced tissue factor (TF) procoagulant activity (PCA) on the surface of cancer cells. Recent studies have shown that TF PCA can be modulated by GRP78, an endoplasmic r ...
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Journal ArticleMod Pathol · January 2010
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Cell surface expression of glucose-regulated protein 78 (GRP78) occurs in several types of cancer; however, its role in the behavior of primary cutaneous melanoma is not well studied. The association of cell surface GRP78 with other proteins such as MTJ1 s ...
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Journal ArticleAntioxid Redox Signal · September 2009
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The 78 kDa glucose-regulated protein (GRP78) is an endoplasmic reticulum chaperone, whose function is generally thought to be restricted to controlling the structural maturation of nascent glycoproteins. However, GRP78 also is expressed on the cell surface ...
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Journal ArticleFront Biosci · January 1, 2008
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Binding of plasminogen (Pg) to cell-surface receptors colocalized with plasminogen activators promotes Pg activation and enables cells to utilize the proteolytic activity of plasmin (Pm). Proteolysis by Pm is necessary in several physiological and patholog ...
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Journal ArticleJ Biol Chem · November 9, 2007
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Both the voltage-dependent anion channel and the glucose-regulated protein 78 have been identified as plasminogen kringle 5 receptors on endothelial cells. In this study, we demonstrate that kringle 5 binds to a region localized in the N-terminal domain of ...
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Journal ArticleCancer Res · December 1, 2006
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Circulating autoantibodies against the glucose-regulated protein of 78 kDa (GRP78) are present at high levels in prostate cancer patients and are a biomarker of aggressive tumor behavior. We purified the anti-GRP78 IgGs and examined their effect on 1-LN, P ...
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Journal ArticleJ Rheumatol · November 2005
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OBJECTIVE: To assess the enzymatic activity and biochemical status of dipeptidyl peptidase IV (DPP IV), an enzyme that participates in the degradation of proinflammatory molecules, in sera from a group of patients with rheumatoid arthritis (RA; n = 15) tre ...
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Journal ArticleJ Cell Biochem · October 1, 2005
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Tumor growth requires the development of new vessels that sprout from pre-existing normal vessels in a process known as "angiogenesis" [Folkman (1971) N Engl J Med 285:1182-1186]. These new vessels arise from local capillaries, arteries, and veins in respo ...
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Journal ArticleJ Biol Chem · July 22, 2005
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Binding of plasminogen type II (Pg 2) to dipeptidyl peptidase IV (DPP IV) on the surface of the highly invasive 1-LN human prostate tumor cell line induces an intracellular Ca2+ ([Ca2+]i) signaling cascade accompanied by a rise in intracellular pH (pHi). I ...
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Journal ArticleJ Immunol · February 15, 2005
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MTJ-1 associates with a glucose-regulated protein of Mr approximately 78,000(GRP78) in the endoplasmic reticulum and modulates GRP78 activity as a chaperone. GRP78 also exists on the cell surface membrane, where it is associated with a number of functions. ...
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Journal ArticleExp Cell Res · February 1, 2005
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Previous studies demonstrate that one of the six plasminogen type 2 glycoforms, plasminogen 2epsilon, enhances invasiveness of the 1-LN human prostate tumor cell line in an in vitro model. Binding of plasminogen 2epsilon to CD26 on the cell surface induces ...
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Journal ArticleClin Exp Rheumatol · 2005
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OBJECTIVES: Lipoteichoic acid (LTA), induces some of the clinical symptoms of Behçet's disease (BD) in a rat animal model. These results led to the hypothesis that LTA may also trigger BD in humans. We investigated the humoral and cellular immune response ...
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Journal ArticleCell Signal · August 2004
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The activated proteinase inhibitor alpha2-macroglobulin (alpha2M*) binds to two receptors, the low density lipoprotein receptor-related protein (LRP-1) and the alpha2M* signalling receptor (alpha2MSR). Silencing LRP-1 gene expression in macrophages by RNA ...
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Journal ArticleJ Biol Chem · May 14, 2004
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Adenosine deaminase (ADA) is expressed intracellularly by all cells, but in some tissues, it is also associated with the cell surface multifunctional glycoprotein CD26/dipeptidyl peptidase IV. By modulating extracellular adenosine, this "ecto-ADA" may regu ...
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Journal ArticleJ Biol Chem · July 18, 2003
Human plasminogen contains structural domains that are termed kringles. Proteolytic cleavage of plasminogen yields kringles 1-3 or 4 and kringle 5 (K5), which regulate endothelial cell proliferation. The receptor for kringles 1-3 or 4 has been identified a ...
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Journal ArticleClin Diagn Lab Immunol · November 2002
Dipeptidyl peptidase IV (DPP IV) (CD26) plays a critical role in the modulation and expression of autoimmune and inflammatory diseases. We recently reported that sera from patients with rheumatoid arthritis and systemic lupus erythematosus contained low le ...
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Journal ArticleJ Biol Chem · November 1, 2002
The low density lipoprotein receptor-related protein (LRP) is a scavenger receptor that binds to many proteins, some of which trigger signal transduction. Receptor-recognized forms of alpha(2)-Macroglobulin (alpha(2)M*) bind to LRP, but the pattern of sign ...
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Journal ArticleBlood · June 15, 2002
Tissue factor (TF), the initiator of the extrinsic pathway of coagulation, binds plasminogen (Pg) with high affinity through an interaction between kringles 1-3 of Pg and the extracellular domain of TF. We investigated the binding of Pg type 1 (Pg 1) and P ...
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Journal ArticleBiochem J · April 15, 2001
Both plasminogen (Pg) activation and matrix metalloproteinases (MMPs) are involved in the proteolytic degradation of extracellular matrix components, a requisite event for malignant cell metastasis. The highly invasive 1-LN human prostate tumour cell line ...
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Journal ArticleClin Exp Rheumatol · 2001
OBJECTIVES: To assess the serum levels, specific activity and other characteristics of dipeptidylpeptidase IV (DPP IV/CD26), an ectoenzyme that plays a critical role in the modulation and expression of autoimmune and inflammatory diseases, from patients wi ...
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Journal ArticleArch Biochem Biophys · November 1, 2000
Cellular binding of receptor-recognized forms of alpha2-macroglobulin (alpha2M*) is mediated by the low-density lipoprotein receptor related protein (LRP) and the alpha2M signaling receptor (alpha2MSR). In nonmalignant cells, ligation of alpha2MSR promotes ...
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Journal ArticleJ Biol Chem · September 3, 1999
We have studied insulin-dependent regulation of macrophage alpha(2)-macroglobulin signaling receptors (alpha(2)MSR) and low density lipoprotein receptor-related protein/alpha(2)M receptors (LRP/alpha(2)MR) employing cell binding of (125)I-alpha(2)M*, inhib ...
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Journal ArticleFASEB Journal · December 1, 1998
In 1984 this laboratory showed that the treatment of adipocytes and fibrob lasts with insulin enhanced the binding of 125I-a2M-methylamine by about 2-3 fold and its slowed receptor-mediated degradation. We have recently reported the presence of a novel ojM ...
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Journal ArticleFASEB Journal · December 1, 1998
Remodeling of the extracellular matrix (ECM), which occurs during metastatic processes, is one of the requisite events for cellular invasion. Both the plasminogen (Pg) activation system and matrix metalloproteinases (MMPs) are involved in proteolytic degra ...
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Journal ArticleFibrinolysis and Proteolysis · January 1, 1998
Plasminogen (Pg) binds to synovial fibroblasts from patients with rheumatoid arthritis with a very high affinity and in a dose-dependent manner. The Pg receptor in these cells is composed of a glycoprotein IIb/IIIa related protein (α(IIIb)β3) in associatio ...
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Journal ArticleFibrinolysis and Proteolysis · January 1, 1998
Objective: To assess the reactivity between dipeptidyl peptidase IV (DPP IV) and the α2,3-linked sialic acid of the plasminogen (Pg)Thr345 O- linked carbohydrate chain as the mechanism enabling plasmin (Pm) to induce intracellular Ca2+ via DPP IV on rheuma ...
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Journal ArticleJ Mol Med (Berl) · May 1997
Plasminogen (Pg) in the synovial fluid of patients with acute inflammatory disease, including rheumatoid arthritis, osteoarthritis, and gout, was purified by affinity chromatography techniques. The Pg isolated from patients with osteoarthritis and gout has ...
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Journal ArticleJ Biol Chem · January 3, 1997
In the present study, we demonstrate that the alpha2-macroglobulin (alpha2M) signaling receptor is up-regulated on rheumatoid synovial fibroblasts. In rheumatoid cells, 125I-alpha2M-methylamine bound to two sites; namely, one of high affinity (Kd approxima ...
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Journal ArticleJ Mol Med (Berl) · August 1996
Sera from patients with rheumatoid arthritis containing high titers of anti-streptokinase antibodies were found to contain anti-plasminogen antibodies of the IgG and IgA classes. High titers of anti-plasminogen autoantibodies of the IgA class were also fou ...
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Journal ArticleBiochem J · January 1, 1996
Streptokinase, an extracellular protein produced by Streptococci, is capable of activating the human fibrinolytic zymogen plasminogen. The rate of amidolytic activity of the plasminogen-streptokinase complex is greatly diminished by micromolar concentratio ...
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Journal ArticleJ Rheumatol · January 1996
OBJECTIVE: Fibronectin (FN) and the streptococcal plasminogen activator streptokinase (SK) share the epitope LTSRPA. This epitope is not reactive in native FN and it reacts with anti-SK antibodies only after plasmin digestion of the protein. To investigate ...
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Journal ArticleFibrinolysis · January 1, 1996
Both plasminogen (Pg) and the streptococcal plasminogen activator streptokinase (SK) bind to synovial fibroblasts from patients with rheumatoid arthritis (RA) with a very high affinity and in a dose-dependent manner. The receptor for both proteins has been ...
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Journal ArticleFibrinolysis · January 1, 1996
Receptors which bind plasminogen (Pg) have previously been demonstrated in HUVEC. To determine whether the mechanism by which the Pg fragment, angiostatin, inhibits endothelial cell migralion and/or proliferation involves interaction with the Pg receptor, ...
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Journal ArticleFibrinolysis · January 1, 1996
Plasminogen 2 has six glycoforms that differ in their sialic acid content. In this study we have examined the effect that this differential sialylation has on activation of these glycoforms by streptokinase (SK). We find that increases in sialic acid conte ...
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Journal ArticleFibrinolysis · January 1, 1996
Streptokinase (SK), a potent non-proteolytic plasminogen (Pg) activator, binds to synovial fibroblasts derived from patients with rheumatoid arthritis(RA) at very high affinity (Kd= 77 nM) either directly or via a complex with Pg. By contrast, SK does not ...
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Journal ArticleJ Biol Chem · February 11, 1994
Plasminogen (Pg) activation on the surface of rheumatoid arthritis (RA) synovial fibroblasts by the urinary-type Pg activator induced a significant increase in cytosolic free Ca2+ concentration. This response was not observed in normal synovial fibroblasts ...
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Journal ArticleJ Biol Chem · October 5, 1993
Both plasminogen (Pg) and urinary-type Pg activator (u-PA), but not tissue-type Pg activator (t-PA), bind to normal and rheumatoid arthritis (RA) human synovial fibroblasts in culture with high affinity and in a dose-dependent manner. Single cell intracell ...
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Journal ArticleBiochim Biophys Acta · January 22, 1993
Rheumatoid arthritis is a disease characterized by a destructive inflammatory process in joints. Fibronectin (FN) is present at a high concentration in rheumatoid synovial tissue and it is a chemoattractant for inflammatory cells. FN fragments also play si ...
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Journal ArticleBiochem J · May 15, 1992
There are two major isoenzymes of plasminogen (Pg) in human plasma, designated Pg1 and Pg2. Both Pg forms have an identical primary structure, but differ in their extent of glycosylation. Removal of the oligosaccharide chains alters the normal physiologica ...
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Journal ArticleArch Biochem Biophys · May 1, 1991
Specific cell surface receptors for plasminogen (Pg) are expressed by a wide variety of cell types. The colocalization of receptors for Pg and its activators restricts plasmin (Pm) activity to specific sites and serves to promote fibrinolysis and local Pg ...
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Journal ArticleArch Biochem Biophys · January 1991
The activation of native human plasminogen (Glu1-Pg) by tissue plasminogen activator, urinary plasminogen activator (u-PA), and streptokinase is inhibited by the divalent cations Ca2+, Mg2+, and Mn2+. This inhibition is accompanied by a conformational chan ...
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Journal ArticleBiochim Biophys Acta · July 6, 1990
A cDNA library was constructed in the phage lambda gt11 from human liver mRNA enriched for plasminogen mRNA by chromatography on Sepharose 4B. A full-length cDNA clone of human plasminogen was isolated. The 2.7 kb cDNA encoded the entire plasminogen molecu ...
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Journal ArticleJ Clin Invest · July 1990
Plasminogen isolated from 60 full-term newborns differs from adult plasminogen in carbohydrate composition, kinetic activation constants, and cell binding. Amino acid composition and amino-terminal sequence analysis data indicate that the plasminogens of n ...
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Journal ArticleBiochemistry · May 22, 1990
The kinetics of activation of Glu-plasminogen (Glu-Pg) and Lys77-Pg by two-chain recombinant tissue plasminogen activator (t-PA) were determined in the presence of isolated protein components of the extracellular matrix (ECM) and compared to activation in ...
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Journal ArticleBiochemistry · March 21, 1989
Lipoprotein a [Lp(a)] inhibits human plasminogen (Pg) conversion to plasmin (Pm) by streptokinase- (SK-) mediated activation. Kinetic and binding studies indicate that Lp(a) inhibits Pg activation by competitive and uncompetitive inhibition. Lp(a) competes ...
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Journal ArticleBiochemistry · March 21, 1989
Specific cell surface receptors for plasminogen (Pg) are expressed by a wide variety of cell types and serve to promote fibrinolysis and local Pg proteolysis. Pg types 1 and 2, separated by chromatography on concanavalin A-Sepharose, were utilized to deter ...
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Journal ArticleBiochemistry · January 17, 1984
mRNA was isolated from total RNA of monkey liver by oligo(dT)-cellulose chromatography and was translated in a rabbit reticulocyte cell-free system. Analysis of the translation products immunoprecipitated with specific antibodies to monkey plasma plasminog ...
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Journal ArticleJ Biol Chem · February 25, 1978
The object of this investigation was to distinguish between two potential mechanisms of activation of human plasminogen (HPg) to plasmin (HPm) by catalytic levels of the activator complex, streptokinase.plasmin (SK.HPm). One mechanism, which is widely supp ...
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Journal ArticleJ Biol Chem · April 10, 1977
The heavy polypeptide chains of human Glu-plasmin and human Lys-plasmin have been isolated in native solvents, after partial reduction and carboxymethylation of the corresponding plasmins. Two major forms of each heavy chain can be eluted, after adsorption ...
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