20 results on '"Vocca, I"'
Search Results
2. Peripheral blood immune response elicited by beta-lactoglobulin in childhood cow's milk allergy
- Author
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Vocca I., BERNI CANANI, ROBERTO, CAMARCA, ALESSANDRA, Ruotolo S., Nocerino R., Radano G., Del Mastro A., TRONCONE, RICCARDO, Gianfrani C., Vocca, I., BERNI CANANI, Roberto, Camarca, Alessandra, Ruotolo, S., Nocerino, R., Radano, G., Del Mastro, A., Troncone, Riccardo, and Gianfrani, C.
- Published
- 2011
3. MECCANISMI DI ACQUISIZIONE DELLA TOLLERANZA AD ANTIGENI ALIMENTARI: STUDIO DELLA RISPOSTA IMMUNOLOGICA SPECIFICA ALLA BETA-LATTOGLOBULINA IN BAMBINI CON ALLERGIA ALLE PROTEINE DEL LATTE VACCINO
- Author
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Ruotolo S., Vocca I., Camarca A., Tardi M., Nocerino R., Troncone R., Gianfrani C., BERNI CANANI, ROBERTO, Ruotolo, S., Vocca, I., Camarca, A., Tardi, M., Nocerino, R., Troncone, R., Gianfrani, C., and BERNI CANANI, Roberto
- Published
- 2009
4. Urokinase receptor activation by a novel interaction between connecting peptide region of Urokinase and αvβ5 Integrin Journal of Cell Science, 119, 3424-3434, 2006
- Author
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FRANCO, P, VOCCA, I, CARRIERO, M. V, ALFANO, D, CITO, L, LONGANESI CATTANI, I, P, OSSOWSKI, L, STOPPELLI, M. P., GRIECO, PAOLO, Franco, P, Vocca, I, Carriero, M. V, Alfano, D, Cito, L, Longanesi, Cattani, I, Grieco, Paolo, P, Ossowski, L, Stoppelli, and M., P.
- Subjects
Urokinase ,Peptide Synthesis - Abstract
The serine protease urokinase (uPA) binds to the urokinase receptor (uPAR) through its growth-factor domain (GFD, residues 1-49), affecting cell migration, adhesion and growth. Here, we show that uPA can promote cytoskeletal rearrangements and directional cell migration in a GFD-independent manner, through a new and specific interaction between an internal uPA domain coined 'connecting peptide' (residues 132-158) and cell-surface integrin alpha v beta 5. Remarkably, a peptide corresponding to this region (CPp, residues 135-158) retains the ability to bind to alpha v beta 5, eliciting cytoskeletal rearrangements and directing cell migration at a concentration as low as 1-10 pM. These effects are lost in cells not expressing uPAR, indicating that the uPAR is required for CPp-dependent signaling. Furthermore, the CPp-alpha v beta 5-integrin interaction enhances F-actin-enriched protrusions and cell migration induced by the well-established interaction between the uPAR-binding peptide (GFDp, residues 12-32) of uPA and uPAR. These results provide new insight into the function of uPA, which - through individual domains - can engage two different surface receptors (uPAR and alpha v beta 5 integrin), thus initiating and potentiating intracellular signaling and migration.
- Published
- 2006
5. Immunological evaluation of the alcohol-soluble protein fraction from Gluten-Free Grains in Relation to Celiac Disease
- Author
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Bergamo P, Maurano F, Mazzarella G, Vocca I, Rivelli A, De Falco E, Gianfrani C, and Rossi M.
- Subjects
embryonic structures ,nutritional and metabolic diseases ,food and beverages - Abstract
Celiac disease (CD) is a gluten-sensitive enteropathy with an immune basis. We established the immune reactivity of the alcohol-soluble fraction from two minor cereals (tef and millet) and two pseudocereals (amaranth and quinoa) which are believed to be nontoxic based on taxonomy. Grains were examined in intestinal T-cell lines (iTCLs), cultures of duodenal explants from HLA-DQ21 CD patients and HLA-DQ8 transgenic mice for signs of activation. Our data indicated that tef, millet, amaranth, and quinoa did not show any immune crossreactivity toward wheat gliadin, and therefore confirming their safety in the diet of CD patients.
- Published
- 2011
6. Inhibition of migration and invasion of carcinoma cells by urokinase-derived antagonists of alphavbeta5 integrin activation
- Author
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Vocca I, Franco P, Alfano D, Votta G, Carriero MV, Estrada Y, Caputi M, Netti PA, Ossowski L, and Stoppelli MP
- Published
- 2009
7. CCNA1 (cyclin A1)
- Author
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Vocca, I, primary, Muzi, G, additional, Pentimalli, F, additional, and Giordano, A, additional
- Published
- 2012
- Full Text
- View/download PDF
8. ID: 341 Urokinase receptor activation by a novel interaction between connecting peptide region of urokinase and alphavbeta5 integrin
- Author
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Vocca, I., primary, Franco, P., additional, Carriero, M., additional, Alfano, D., additional, Longanesi-Cattani, I., additional, Ossowski, L., additional, and Stoppelli, M., additional
- Published
- 2006
- Full Text
- View/download PDF
9. Immunogenicity of Monococcum wheat in Celiac Patients
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Salvatore Auricchio, Nicola Giardullo, Riccardo Troncone, Norberto Pogna, Giuseppe Mazzarella, Gaetano Iaquinto, Mariatonia Maglio, Vera Rotondi Aufiero, Carmen Gianfrani, Alessandra Camarca, Immacolata Vocca, Gianfrani, Carmela, Maglio, Mariantonia, Rotondi Aufiero, V, Camarca, Alessandra, Vocca, I, Iaquinto, G, Giardullo, N, Pogna, N, Troncone, Riccardo, Auricchio, Salvatore, and Mazzarella, G.
- Subjects
Triticum monococcum ,Nutrition and Dietetics ,biology ,celiac ,Cell growth ,T cell ,Medicine (miscellaneous) ,food and beverages ,Acquired immune system ,Immune system ,medicine.anatomical_structure ,Antigen ,Interleukin 15 ,Immunology ,biology.protein ,medicine ,Intraepithelial lymphocyte ,Gliadin ,innate immunity - Abstract
Background: Research is intense to find wheat of low or null toxicity for patients with celiac disease (CD). Among candidates, there are diploid wheat species. Objective: We compared the immunological properties of 2 lines of diploid monococcum wheat (Triticum monococcum ssp. monococcum), Monlis and ID331, with those of common wheat (Triticum aestivum). Design: Interferon-g production and the proliferation of intestinal gliadin-specific T cell lines and clones were measured as evidence of T cell activation by peptic and tryptic (PT) digests of gliadins from 2 monococcum lines. Furthermore, organ cultures of jejunal biopsies from 28 CD patients were set up to assess the effects of PT gliadin on innate and adaptive immune response by using immunohistochemistry. Results: Monlis and ID331 induced interferon-g production and proliferation in celiac mucosal T cells. In organ cultures, Monlis PT digest induced a significant increase of IL-15 epithelial expression and crypt enterocyte proliferation, whereas ID331 had no effect. Both monococcum lines caused intraepithelial T cell infiltration and lamina propria T cell activation. Conclusions: Our data show that the monococcum lines Monlis and ID331 activate the CD T cell response and suggest that these lines are toxic for celiac patients. However, ID331 is likely to be less effective in inducing CD because of its inability to activate the innate immune pathways. Am J Clin Nutr 2012;96:1339‐45.
- Published
- 2012
10. Peripheral blood immune response elicited by beta-lactoglobulin in childhood cow's milk allergy
- Author
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Alessandra Camarca, Carmen Gianfrani, Andrea Del Mastro, Rita Nocerino, Roberto Berni Canani, Giorgia Radano, S. Ruotolo, Riccardo Troncone, Immacolata Vocca, Vocca, I, BERNI CANANI, Roberto, Camarca, Alessandra, Ruotolo, S, Nocerino, Rita, Radano, G, DEL MASTRO, A, Troncone, Riccardo, and Gianfrani, C.
- Subjects
Hypersensitivity, Immediate ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Milk allergy ,Lactoglobulins ,Biology ,Peripheral blood mononuclear cell ,Statistics, Nonparametric ,Interferon-gamma ,Immune system ,Th2 Cells ,Internal medicine ,medicine ,Animals ,Humans ,Child ,Cell Proliferation ,Interleukin-13 ,Cell growth ,Case-control study ,Age Factors ,Infant ,medicine.disease ,In vitro ,Interleukin-10 ,Endocrinology ,Cytokine ,Milk ,Cell culture ,Case-Control Studies ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Immunology ,Leukocytes, Mononuclear ,Female ,Interleukin-4 ,Milk Hypersensitivity - Abstract
Several studies analyzing the immune responses in patients with cow's milk allergy (CMA) have used T-cell lines or T-cell clones that require prolonged in vitro cell culturing and may result in a switched cell phenotype and function. We investigated immune responses to beta-lactoglobulin (b-LG) in peripheral blood mononuclear cells after a short in vitro antigen stimulation in children with acute CMA (both IgE-mediated and non-IgE-mediated forms) and in those who outgrew an IgE-mediated CMA. Healthy controls were also investigated. Peripheral blood mononuclear cells were assayed for IL-13, IFN-γ, IL-4, and IL-10. Although b-LG induced a cytokine production and/or cell proliferation almost in all children, included healthy controls, differences were observed among the four groups. Children with IgE-mediated CMA had a marked Th2-response, with high IL-13 production and proliferation, but low IFN-γ; by contrast, children with non-IgE-mediated CMA produced no, or very low, IL-13 and cell proliferation. Children, who outgrew CMA, showed a shift to a Th1-response, with reduced IL-13 and increased IFN-γ. IL-10-responses were high in all groups, with the highest level in healthy children; by contrast, IL-4 was undetectable in all children. This study highlights the use of shortly stimulated peripheral blood cells to investigate the food-induced immune responses.
- Published
- 2011
11. Inhibition of migration and invasion of carcinoma cells by urokinase-derived antagonists of alphavbeta5 integrin activation
- Author
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Mario Caputi, Paola Franco, Maria Vincenza Carriero, Immacolata Vocca, Yeriel Estrada, Maria Patrizia Stoppelli, Giuseppina Votta, Paolo A. Netti, Daniela Alfano, Liliana Ossowski, Vocca, I, Franco, P, Alfano, D, Votta, G, Carriero, M, Estrada, Y, Caputi, M, Netti, P, Ossowski, L, Stoppelli, M, Carriero, Mv, Netti, PAOLO ANTONIO, and Stoppelli, Mp
- Subjects
cell migration inhibitor ,Talin ,Cancer Research ,Integrins ,Integrin ,αVβ5 antagonist ,Models, Biological ,Cell Movement ,Cell Line, Tumor ,cell cytoskeleton ,Humans ,Neoplasm Invasiveness ,Receptors, Vitronectin ,Gene Silencing ,Cytoskeleton ,uPA phosphorylation ,biology ,Cell adhesion molecule ,in vivo carcinoma invasion ,Chemotaxis ,Carcinoma ,Cell migration ,avb5 antagonist ,Urokinase-Type Plasminogen Activator ,Cell biology ,Squamous carcinoma ,Protein Structure, Tertiary ,Urokinase receptor ,Oncology ,Epidermoid carcinoma ,Cancer cell ,Mutation ,Cancer research ,biology.protein ,Vitronectin - Abstract
We previously showed that, while binding to urokinase receptor (uPAR) through its growth factor domain (GFD, residues 1-49), urokinase (uPA) can engage alphavbeta5 integrin through an internal domain (CP, residues 132-158). This novel uPA/alphavbeta5 interaction promotes cytoskeletal rearrangements and directional cell migration (Franco et al., J Cell Sci 2006;119:3424-34). We now show that treatment of cells with phosphomimic uPA (uPA138E/303E, serine 138 and 303 substituted with glutamic acid) strongly inhibits matrix-induced cell migration. Unlike uPA, binding of uPA138E/303E to cell surface did not induce F-actin enriched protruding structures and caused a 5-fold reduction in cell translocation speed, as determined by video tracking of living cells. Inhibition of migration was found to be independent of uPAR, since uPA variants lacking the GFD domain, but carrying the relevant Ser to Glu substitutions were as effective inhibitor as uPA138E/303E. Through several independent approaches, we established that the phosphomimics specifically bind to alphavbeta5 integrin through the CP region carrying the S138E mutation. This interaction blocks integrin activation, as determined by a decreased affinity of alphavbeta5 to vitronectin and a reduced association of the beta5 cytoplasmic tail with talin. Finally, stable expression of uPA138E/303E in human squamous carcinoma cells prevented tumor cell invasion in vivo. Thus, when expressed in cancer cells, the inhibitory phosphomimic effect was dominant over the effect of endogenously produced uPA. These results shed light on the regulation of cell migration by uPA phosphorylation and provide a realistic opportunity for a novel antiinvasive/metastatic therapeutic intervention.
- Published
- 2008
12. The urokinase plasminogen activator and its receptor: role in cell growth and apoptosis
- Author
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Mario Caputi, Ingram Iaccarino, Maria Patrizia Stoppelli, Paola Franco, Daniela Alfano, Alessandro Mancini, Maria Vincenza Carriero, Viviana Pisa, Nadia Gambi, Immacolata Vocca, Alfano, D., Franco, P., Vocca, I., Gambi, N., Pisa, V., Mancini, Alessandro, Caputi, M., Carriero, M., Iaccarino, I., and Stoppelli, M.
- Subjects
Urokinase ,Cell growth ,Activator (genetics) ,Plasmin ,urinary-type plasminogen activator ,apoptosis ,Cell migration ,Hematology ,Biology ,Cell biology ,Urokinase receptor ,EGF-like domain ,cell proliferation ,Biochemistry ,medicine ,urokinase receptor ,tumour progression ,Signal transduction ,Plasminogen activator ,medicine.drug - Abstract
SummaryThe urinary-type plasminogen activator, or uPA, controls matrix degradation through the conversion of plasminogen into plasmin and is regarded as the critical trigger for plasmin generation during cell migration and invasion, under physiological and pathological conditions (such as cancer metastasis).The proteolytic activity of uPA is responsible for the activation or release of several growth factors and modulates the cell survival/apoptosis ratio through the dynamic control of cell-matrix contacts. The urokinase receptor (uPAR), binding to the EGF-like domain of uPA, directs membrane-associated extracellular proteolysis and signals through transmembrane proteins, thus regulating cell migration, adhesion and cytoskeletal status. However, recent evidence highlights an intricate relationship linking the uPA/uPAR system to cell growth and apoptosis.
- Published
- 2005
- Full Text
- View/download PDF
13. RB1 dual role in proliferation and apoptosis: cell fate control and implications for cancer therapy.
- Author
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Indovina P, Pentimalli F, Casini N, Vocca I, and Giordano A
- Subjects
- Animals, Antineoplastic Agents therapeutic use, Biomarkers, Tumor genetics, Gene Expression Regulation, Neoplastic, Humans, Molecular Targeted Therapy, Neoplasms drug therapy, Neoplasms genetics, Neoplasms pathology, Phosphorylation, Retinoblastoma Protein genetics, Signal Transduction, Treatment Outcome, Apoptosis drug effects, Biomarkers, Tumor metabolism, Cell Proliferation drug effects, Neoplasms metabolism, Retinoblastoma Protein metabolism
- Abstract
Inactivation of the retinoblastoma (RB1) tumor suppressor is one of the most frequent and early recognized molecular hallmarks of cancer. RB1, although mainly studied for its role in the regulation of cell cycle, emerged as a key regulator of many biological processes. Among these, RB1 has been implicated in the regulation of apoptosis, the alteration of which underlies both cancer development and resistance to therapy. RB1 role in apoptosis, however, is still controversial because, depending on the context, the apoptotic cues, and its own status, RB1 can act either by inhibiting or promoting apoptosis. Moreover, the mechanisms whereby RB1 controls both proliferation and apoptosis in a coordinated manner are only now beginning to be unraveled. Here, by reviewing the main studies assessing the effect of RB1 status and modulation on these processes, we provide an overview of the possible underlying molecular mechanisms whereby RB1, and its family members, dictate cell fate in various contexts. We also describe the current antitumoral strategies aimed at the use of RB1 as predictive, prognostic and therapeutic target in cancer. A thorough understanding of RB1 function in controlling cell fate determination is crucial for a successful translation of RB1 status assessment in the clinical setting.
- Published
- 2015
- Full Text
- View/download PDF
14. Immunogenicity of monococcum wheat in celiac patients.
- Author
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Gianfrani C, Maglio M, Rotondi Aufiero V, Camarca A, Vocca I, Iaquinto G, Giardullo N, Pogna N, Troncone R, Auricchio S, and Mazzarella G
- Subjects
- Adolescent, Adult, Antigens, Plant analysis, Antigens, Plant metabolism, Celiac Disease diet therapy, Celiac Disease metabolism, Celiac Disease pathology, Cell Proliferation, Cells, Cultured, Child, Child, Preschool, Clone Cells, Diploidy, Flour analysis, Gliadin analysis, Gliadin metabolism, Humans, Interferon-gamma Release Tests, Intestinal Mucosa metabolism, Intestinal Mucosa pathology, Intestine, Small immunology, Intestine, Small metabolism, Intestine, Small pathology, Lymphocyte Activation, Middle Aged, Protein Hydrolysates adverse effects, Protein Hydrolysates analysis, Protein Hydrolysates metabolism, Species Specificity, T-Lymphocytes immunology, T-Lymphocytes metabolism, T-Lymphocytes pathology, Tissue Culture Techniques, Triticum chemistry, Triticum genetics, Young Adult, Antigens, Plant adverse effects, Celiac Disease immunology, Flour adverse effects, Gliadin adverse effects, Intestinal Mucosa immunology, Triticum adverse effects
- Abstract
Background: Research is intense to find wheat of low or null toxicity for patients with celiac disease (CD). Among candidates, there are diploid wheat species., Objective: We compared the immunological properties of 2 lines of diploid monococcum wheat (Triticum monococcum ssp. monococcum), Monlis and ID331, with those of common wheat (Triticum aestivum)., Design: Interferon-γ production and the proliferation of intestinal gliadin-specific T cell lines and clones were measured as evidence of T cell activation by peptic and tryptic (PT) digests of gliadins from 2 monococcum lines. Furthermore, organ cultures of jejunal biopsies from 28 CD patients were set up to assess the effects of PT gliadin on innate and adaptive immune response by using immunohistochemistry., Results: Monlis and ID331 induced interferon-γ production and proliferation in celiac mucosal T cells. In organ cultures, Monlis PT digest induced a significant increase of IL-15 epithelial expression and crypt enterocyte proliferation, whereas ID331 had no effect. Both monococcum lines caused intraepithelial T cell infiltration and lamina propria T cell activation., Conclusions: Our data show that the monococcum lines Monlis and ID331 activate the CD T cell response and suggest that these lines are toxic for celiac patients. However, ID331 is likely to be less effective in inducing CD because of its inability to activate the innate immune pathways.
- Published
- 2012
- Full Text
- View/download PDF
15. Shotgun proteome analysis of beer and the immunogenic potential of beer polypeptides.
- Author
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Picariello G, Mamone G, Nitride C, Addeo F, Camarca A, Vocca I, Gianfrani C, and Ferranti P
- Subjects
- Adolescent, Adult, Amino Acid Sequence, Celiac Disease immunology, Child, Child, Preschool, Chromatography, High Pressure Liquid, Glutens analysis, Hordeum chemistry, Humans, Molecular Sequence Data, Peptides analysis, Plant Proteins analysis, Prolamins analysis, Saccharomyces cerevisiae Proteins immunology, Spectrometry, Mass, Electrospray Ionization, T-Lymphocytes immunology, Allergens analysis, Beer analysis, Glutens immunology, Peptides immunology, Proteome analysis
- Abstract
The majority of beer proteins originate from barley (Hordeum vulgare) which is used for brewing. Barley is known to contain celiacogenic gliadin-like prolamins (hordeins) along with other immunogenic proteins which endure malt proteases and the harsh conditions of brewing. In addition, a multitude of peptides that may retain or even amplify the immune-stimulating potential is released in beer because of proteolysis. The comprehensive annotation of the beer proteome is challenged both by the high concentration range of the protein entities and by a severe degree of processing-induced modifications. Overcoming the pitfalls of the classical two-dimensional electrophoresis approach coupled to mass spectrometry (MS), the gel-free shotgun proteomic analysis expanded the current inventory of a popular Italian beer to 33 gene products, including traces of intact B- and D-hordeins and 10 proteins from Saccharomyces spp. The high performance liquid chromatography-electrospray MS/MS peptidomic analysis of the low-molecular weight beer components disclosed a panel of hordein-derived peptides that encrypt gluten-like sequence motifs, potentially harmful to celiacs. The presence of antigliadin IgA-immunoresponsive prolamins was assayed by Western and dot blot using sera of N=4 celiac patients. Gliadin-reactive T-cell lines isolated from the intestine of N=5 celiacs activated an IFN-γ response when challenged with deamidated beer polypeptides., (Copyright © 2012 Elsevier B.V. All rights reserved.)
- Published
- 2012
- Full Text
- View/download PDF
16. Peripheral blood immune response elicited by beta-lactoglobulin in childhood cow's milk allergy.
- Author
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Vocca I, Canani RB, Camarca A, Ruotolo S, Nocerino R, Radano G, Del Mastro A, Troncone R, and Gianfrani C
- Subjects
- Age Factors, Animals, Case-Control Studies, Cell Proliferation drug effects, Child, Child, Preschool, Female, Humans, Hypersensitivity, Immediate chemically induced, Infant, Interferon-gamma metabolism, Interleukin-10 metabolism, Interleukin-13 metabolism, Interleukin-4 metabolism, Lactoglobulins immunology, Leukocytes, Mononuclear drug effects, Leukocytes, Mononuclear metabolism, Male, Statistics, Nonparametric, Th2 Cells immunology, Th2 Cells metabolism, Hypersensitivity, Immediate immunology, Lactoglobulins pharmacology, Leukocytes, Mononuclear immunology, Milk adverse effects, Milk Hypersensitivity immunology
- Abstract
Several studies analyzing the immune responses in patients with cow's milk allergy (CMA) have used T-cell lines or T-cell clones that require prolonged in vitro cell culturing and may result in a switched cell phenotype and function. We investigated immune responses to beta-lactoglobulin (b-LG) in peripheral blood mononuclear cells after a short in vitro antigen stimulation in children with acute CMA (both IgE-mediated and non-IgE-mediated forms) and in those who outgrew an IgE-mediated CMA. Healthy controls were also investigated. Peripheral blood mononuclear cells were assayed for IL-13, IFN-γ, IL-4, and IL-10. Although b-LG induced a cytokine production and/or cell proliferation almost in all children, included healthy controls, differences were observed among the four groups. Children with IgE-mediated CMA had a marked Th2-response, with high IL-13 production and proliferation, but low IFN-γ; by contrast, children with non-IgE-mediated CMA produced no, or very low, IL-13 and cell proliferation. Children, who outgrew CMA, showed a shift to a Th1-response, with reduced IL-13 and increased IFN-γ. IL-10-responses were high in all groups, with the highest level in healthy children; by contrast, IL-4 was undetectable in all children. This study highlights the use of shortly stimulated peripheral blood cells to investigate the food-induced immune responses.
- Published
- 2011
- Full Text
- View/download PDF
17. Structure, function and antagonists of urokinase-type plasminogen activator.
- Author
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Vincenza Carriero M, Franco P, Vocca I, Alfano D, Longanesi-Cattani I, Bifulco K, Mancini A, Caputi M, and Stoppelli MP
- Subjects
- Catalytic Domain, Enzyme Inhibitors pharmacology, Humans, Kringles, Models, Molecular, Protein Conformation, Structure-Activity Relationship, Urokinase-Type Plasminogen Activator antagonists & inhibitors, Urokinase-Type Plasminogen Activator chemistry, Urokinase-Type Plasminogen Activator metabolism
- Abstract
Urokinase (uPA) is a serine protease which converts plasminogen to plasmin, a broad-spectrum protease active on extracellular matrix (ECM) components. Like many components of the blood coagulation, fibrinolytic and complement cascades, uPA has a modular structure, including three conserved domains: a growth factor-like domain (GFD, residues 1 - 49), a kringle domain (residues 50 - 131), linked by an interdomain linker or "connecting peptide" (CP, residues 132 - 158) to the serine protease domain (residues 159 - 411). Although direct molecular interactions with urokinase receptor and integrins have been extensively described, the function of single uPA domains is not completely understood. Because of the causal involvment of uPA in cancer invasion and metastasis, the blockade of uPA interactions and activity with specific inhibitors is of interest for novel strategies in cancer therapy. New inhibitors derived from the interdomain linker or "connecting peptide" are coming into focus. This review summarizes the recent findings on the uPA structure-function relationship and provides further information on existing inhibitors of uPA multiple functions.
- Published
- 2009
- Full Text
- View/download PDF
18. Activation of urokinase receptor by a novel interaction between the connecting peptide region of urokinase and alpha v beta 5 integrin.
- Author
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Franco P, Vocca I, Carriero MV, Alfano D, Cito L, Longanesi-Cattani I, Grieco P, Ossowski L, and Stoppelli MP
- Subjects
- Actins metabolism, Animals, Cells, Cultured, Chemotaxis, Humans, Kidney metabolism, Mice, Receptors, Urokinase Plasminogen Activator, Signal Transduction, U937 Cells, Cell Movement, Integrins metabolism, Peptide Fragments metabolism, Receptors, Cell Surface metabolism, Receptors, Vitronectin metabolism, Urokinase-Type Plasminogen Activator metabolism
- Abstract
The serine protease urokinase (uPA) binds to the urokinase receptor (uPAR) through its growth-factor domain (GFD, residues 1-49), affecting cell migration, adhesion and growth. Here, we show that uPA can promote cytoskeletal rearrangements and directional cell migration in a GFD-independent manner, through a new and specific interaction between an internal uPA domain coined ;connecting peptide' (residues 132-158) and cell-surface integrin alpha v beta 5. Remarkably, a peptide corresponding to this region (CPp, residues 135-158) retains the ability to bind to alpha v beta 5, eliciting cytoskeletal rearrangements and directing cell migration at a concentration as low as 1-10 pM. These effects are lost in cells not expressing uPAR, indicating that the uPAR is required for CPp-dependent signaling. Furthermore, the CPp-alpha v beta 5-integrin interaction enhances F-actin-enriched protrusions and cell migration induced by the well-established interaction between the uPAR-binding peptide (GFDp, residues 12-32) of uPA and uPAR. These results provide new insight into the function of uPA, which--through individual domains--can engage two different surface receptors (uPAR and alpha v beta 5 integrin), thus initiating and potentiating intracellular signaling and migration.
- Published
- 2006
- Full Text
- View/download PDF
19. The urokinase plasminogen activator and its receptor: role in cell growth and apoptosis.
- Author
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Alfano D, Franco P, Vocca I, Gambi N, Pisa V, Mancini A, Caputi M, Carriero MV, Iaccarino I, and Stoppelli MP
- Subjects
- Apoptosis, Cell Proliferation, Humans, Receptors, Urokinase Plasminogen Activator, Signal Transduction, Receptors, Cell Surface physiology, Urokinase-Type Plasminogen Activator physiology
- Abstract
The urinary-type plasminogen activator, or uPA, controls matrix degradation through the conversion of plasminogen into plasmin and is regarded as the critical trigger for plasmin generation during cell migration and invasion, under physiological and pathological conditions (such as cancer metastasis). The proteolytic activity of uPA is responsible for the activation or release of several growth factors and modulates the cell survival/apoptosis ratio through the dynamic control of cell-matrix contacts. The urokinase receptor (uPAR), binding to the EGF-like domain of uPA, directs membrane-associated extracellular proteolysis and signals through transmembrane proteins, thus regulating cell migration, adhesion and cytoskeletal status. However, recent evidence highlights an intricate relationship linking the uPA/uPAR system to cell growth and apoptosis.
- Published
- 2005
- Full Text
- View/download PDF
20. Inhibition of receptor-dependent urokinase signaling by specific Ser to Glu substitutions.
- Author
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Carriero MV, Franco P, Gargiulo L, Vocca I, Cito L, Fontana L, Iaccarino C, Del Pozzo G, Guardiola J, and Stoppelli MP
- Subjects
- Amino Acid Substitution, Animals, CD4-Positive T-Lymphocytes cytology, CD4-Positive T-Lymphocytes drug effects, Cell Movement drug effects, Cytoskeletal Proteins metabolism, Enzyme Activation drug effects, Female, Glutamic Acid, Humans, Mice, Oncogene Proteins, Viral metabolism, Paxillin, Phosphoproteins metabolism, Protein Binding, Receptors, Cell Surface metabolism, Receptors, Urokinase Plasminogen Activator, Receptors, Vitronectin metabolism, Serine, Tumor Cells, Cultured, Urokinase-Type Plasminogen Activator genetics, Urokinase-Type Plasminogen Activator metabolism, src-Family Kinases, Proto-Oncogene Proteins, Receptors, Cell Surface physiology, Signal Transduction, Urokinase-Type Plasminogen Activator physiology
- Abstract
We have previously reported that phosphorylation of human urokinase on Ser138/303 abolishes its catalytic-independent motogen and proadhesive abilities, whereas receptor binding is not affected. Here we show that substitution of the two relevant serines with glutamic acid residues impairs the ability of urokinase to mobilize a variety of human and mouse cell lines as well as human primary T lymphocytes. Accordingly, urokinase receptor-dependent signaling, leading to cytoskeletal rearrangements and paxillin re-distribution, does not occur in MCF-7 breast carcinoma cells exposed to 'phosphorylation-like' urokinase. Unlike the wild-type form, di-substituted urokinase is unable to induce the physical association of urokinase receptor with alphavbeta5 vitronectin receptor, which is required for MCF-7 urokinase-dependent cell migration. Finally, the di-substituted variant fails to activate p55fgr, a member of the Src tyrosine kinase family, which mediates cell migration and adhesion of U937 myelomonocytic cells. In conclusion, the finding that specific amino acid substitutions strongly interfere with the ability of urokinase to stimulate cell migration, and the associated intracellular events uncover a novel way to regulate urokinase receptor-dependent signaling.
- Published
- 2002
- Full Text
- View/download PDF
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