Binding of Lys-plasminogen to monocytes/macrophages.

Silverstein, Roy L.; Friedlander, Robert J.; Nicholas, Robert L.; Nachman, Ralph L.

doi:10.1172/jci113814

Cited by 49 publications

(38 citation statements)

References 28 publications

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“…There are seven distinct domains in the Pg molecule: an N-terminal peptide (NTP), five kringle domains, and a serine proteinase domain (3). The kringle domains, each comprising ϳ80 amino acids, are double-looped disulfide-bonded structures that contain the lysinebinding sites (LBS) responsible for Pg binding to extracellular matrix molecules (4) and cell receptors (5,6). In addition to the LBS, Pg also has three benzamidine binding sites (BBS), one in K5, a second in the active site of the proteinase domain, and a third unknown site in the Pg proteinase domain (7).…”

Section: Plasminogen (Pg)mentioning

confidence: 99%

Plasminogen Structural Domains Exhibit Different Functions When Associated with Cell Surface GRP78 or the Voltage-dependent Anion Channel

Gonzalez-Gronow

Kaczowka

Payne

et al. 2007

Journal of Biological Chemistry

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Both the voltage-dependent anion channel and the glucoseregulated 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 the glucose-regulated protein 78, whereas microplasminogen does so through the C-terminal domain of the glucose-regulated protein 78. Both plasminogen fragments induce Ca 2؉ signaling cascades; however, kringle 5 acts through voltage-dependent anion channel and microplasminogen does so via the glucose-regulated protein 78. Because trafficking of voltage-dependent anion channel to the cell surface is associated with heat shock proteins, we investigated a possible association between voltage-dependent anion channel and glucose-regulated protein 78 on the surface of 1-LN human prostate tumor cells. We demonstrate that these proteins co-localize, and changes in the expression of the glucoseregulated protein 78 affect the expression of voltage-dependent anion channel. To differentiate the functions of these receptor proteins, either when acting singly or as a complex, we employed human hexokinase I as a specific ligand for voltage-dependent anion channel, in addition to kringle 5. We show that kringle 5 inhibits 1-LN cell proliferation and promotes caspase-7 activity by a mechanism that requires binding to cell surface voltage-dependent anion channel and is inhibited by human hexokinase I. Plasminogen (Pg)2 is a single-chain 92-kDa glycoprotein containing 791 amino acid residues (1, 2). There are seven distinct domains in the Pg molecule: an N-terminal peptide (NTP), five kringle domains, and a serine proteinase domain (3). The kringle domains, each comprising ϳ80 amino acids, are double-looped disulfide-bonded structures that contain the lysinebinding sites (LBS) responsible for Pg binding to extracellular matrix molecules (4) and cell receptors (5, 6). In addition to the LBS, Pg also has three benzamidine binding sites (BBS), one in K5, a second in the active site of the proteinase domain, and a third unknown site in the Pg proteinase domain (7).Pg is the precursor of angiostatins, a group of anti-angiogenic molecules, consisting of kringles 1-3 (K1-3), 1-4, and 1-5, as well as the single kringles 1 (K1), 2, 3, and 5, but not K4 (8 -10). We have extensively studied the functions of K1-3 and K5 on both endothelial and prostate tumor cell lines (11,12). We reported that K5 binding to the voltage-dependent anion channel (VDAC) on the surface of human umbilical vein endothelial cells (HUVEC) interfered with mechanisms controlling the regulation of intracellular Ca 2ϩ producing a decrease in intracellular pH (11). A recent study also suggests, that K5 binds with high affinity to surface-expressed glucose-regulated protein 78 (GRP78) (13). Both VDAC and GRP78 are expressed on the cell surface in lipid rafts (14, 15). Because trafficking of VDAC to the cell membrane is associated with the heat shock proteins GRP75 and HSP70 (16, 17), we hypothesized a possible associatio...

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Section: Plasminogen (Pg)mentioning

confidence: 99%

Plasminogen Structural Domains Exhibit Different Functions When Associated with Cell Surface GRP78 or the Voltage-dependent Anion Channel

Gonzalez-Gronow

Kaczowka

Payne

et al. 2007

Journal of Biological Chemistry

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“…Lys-plasminogen, the plasminmodified form of native Glu-plasminogen, is formed on the cell surface and is preferentially bound by cells. 47,48 Cellular proteins to which plasminogen binds were identified using a monoclonal antiplasminogen IgG. Following incubation with Lys-plasminogen, several bands were observed in a blot of cell lysate and isolated membranes (ϩLys-Plg, Figure 2).…”

Section: Annexin II Comigrates With a Protein That Binds Plasminogen mentioning

confidence: 99%

Plasminogen-mediated matrix invasion and degradation by macrophages is dependent on surface expression of annexin II

Falcone

Borth

Khan

et al. 2001

Blood

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“…In some wells, the binding buffer was supplemented with 20 m M lysine as well. The lysine inhibits specific plasminogen binding to cell surface receptors by associating with the plasminogen domains that mediate the receptor interaction [ 1,3,4,9,10,15]. Specific binding was defined as the difference between total binding (in the absence of lysine) and binding observed in the presence of 20 mM lysine [4,9].…”

Section: Plasminogen Binding Studiesmentioning

confidence: 99%

Plasminogen carbohydrate side chains in receptor binding and enzyme activation: A study of C6 glioma cells and primary cultures of rat hepatocytes

Hall

Gonias

1990

J of Cellular Biochemistry

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The human [Glu1]-plasminogen carbohydrate isozymes, plasminogen type I (Pg 1) and plasminogen type II (Pg 2), were separated by chromatography and studied in cell binding experiments at 4 degrees C with primary cultures of rat hepatocytes and rat C6 glioma cells. In both cell systems, Pg 1 and Pg 2 bound to an equivalent number of receptors, apparently representing the same population of surface molecules. The affinity for Pg 2 was slightly higher. With hepatocytes, the KD for Pg 1 was 3.2 +/- 0.2 microM, and the KD for Pg 2 was 1.9 +/- 0.1 microM, as determined from Scatchard transformations of the binding isotherms. The Bmax was approximately the same for both isozymes. With C6 cells, the KD for Pg 1 was 2.2 +/- 0.1 microM vs. 1.5 +/- 0.2 microM for Pg 2. Again, the Bmax was similar with both isozymes. 125I-Pg 1 and 125I-Pg 2 were displaced from specific binding sites by either nonradiolabeled isozyme. The KI for Pg 2 was slightly lower than the KI for Pg 1 with hepatocytes (0.9 vs. 1.3 microM) and with C6 cells (0.6 vs. 1.1 microM). No displacement was detected with miniplasminogen at concentrations up to 5.0 microM. Activation of Pg 1 and Pg 2 by recombinant two-chain tissue-plasminogen activator (rt-PA) was enhanced by hepatocyte cultures. The enhancing effect was greater with Pg 2. Hepatocyte cultures did not affect the activation of miniplasminogen by rt-PA or the activation of plasminogen by streptokinase. Unlike the hepatocytes, C6 cells did not enhance the activation of plasminogen by rt-PA or streptokinase; however, plasmin generated in the presence of C6 cells reacted less readily with alpha 2-antiplasmin.

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Binding of Lys-plasminogen to monocytes/macrophages.

Abstract: The ability of mononuclear phagocytes to assemble and acti-

Cited by 49 publications

References 28 publications

Plasminogen Structural Domains Exhibit Different Functions When Associated with Cell Surface GRP78 or the Voltage-dependent Anion Channel

Plasminogen Structural Domains Exhibit Different Functions When Associated with Cell Surface GRP78 or the Voltage-dependent Anion Channel

Plasminogen-mediated matrix invasion and degradation by macrophages is dependent on surface expression of annexin II

Plasminogen carbohydrate side chains in receptor binding and enzyme activation: A study of C6 glioma cells and primary cultures of rat hepatocytes

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