Research Topics
Genomes and Genes | S L GoniasSummaryAffiliation: University of Virginia Country: USA Publications
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Publications
Characterization of the interaction between alpha2-macroglobulin and fibroblast growth factor-2: the role of hydrophobic interactionsSmitha Mathew
Department of Pathology, Box 3712, Duke University Medical Center, Durham, NC 27710, USA
Biochem J 374:123-9. 2003..Our results demonstrate that the interactions of FGF-2 with alpha2M* and HSPGs are biochemically distinct, suggesting that different FGF-2 sequences are involved...- LRP1 regulates remodeling of the extracellular matrix by fibroblastsAlban Gaultier
Department of Pathology, University of California San Diego, La Jolla, California 92093, USA
Matrix Biol 29:22-30. 2010..These results demonstrate that LRP1 regulates ECM remodeling principally by repressing pathways that require plasminogen activation by uPA in association with uPAR... - Low density lipoprotein receptor-related protein: regulation of the plasma membrane proteomeSteven L Gonias
Department of Pathology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA
Thromb Haemost 91:1056-64. 2004..Based on these novel activities, LRP-1 emerges as a protein capable of modeling the interface of the cell with its microenvironment... - Cytokeratin 8 functions as a major plasminogen receptor in select epithelial and carcinoma cellsS L Gonias
Department of Pathology, University of Virginia School of Medicine, Charlottesville VA 22908, USA
Front Biosci 6:D1403-11. 2001..This review focuses on the function of K8 as a plasminogen receptor and its potential role in cancer... - Identical or overlapping sequences in the primary structure of human alpha(2)-macroglobulin are responsible for the binding of nerve growth factor-beta, platelet-derived growth factor-BB, and transforming growth factor-betaS L Gonias
Department of Pathology, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA
J Biol Chem 275:5826-31. 2000..Thus, FP3 may inhibit the activity of PDGF-BB... - Plasminogen activator inhibitor 1 functions as a urokinase response modifier at the level of cell signaling and thereby promotes MCF-7 cell growthD J Webb
Department of Pathology, and Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA
J Cell Biol 152:741-52. 2001..The kinetics of ERK phosphorylation in response to uPAR ligation determine the function of uPA and uPA-PAI-1 complex as growth promoters... - Urokinase receptor primes cells to proliferate in response to epidermal growth factorM Jo
Department of Pathology, University of California San Diego, La Jolla, CA, USA
Oncogene 26:2585-94. 2007..We conclude that uPAR-dependent cell-signaling may prime cells to proliferate in response to EGF by promoting Tyr-845 phosphorylation and STAT5b activation. The importance of this pathway depends on the c-Src level in the cell... - Endogenously produced urokinase-type plasminogen activator is a major determinant of the basal level of activated ERK/MAP kinase and prevents apoptosis in MDA-MB-231 breast cancer cellsZ Ma
Department of Pathology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA
J Cell Sci 114:3387-96. 2001..The ability of uPA to signal through uPAR, maintain an elevated basal level of activated ERK and inhibit apoptosis represents a novel mechanism whereby the uPA-uPAR system may affect breast cancer progression in vivo... - Murine alpha-macroglobulins demonstrate divergent activities as neutralizers of transforming growth factor-beta and as inducers of nitric oxide synthesis. A possible mechanism for the endotoxin insensitivity of the alpha2-macroglobulin gene knock-out mousD J Webb
Departments of Pathology and Biochemistry, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA
J Biol Chem 271:24982-8. 1996..Malpha2M is the only murine alpha-macroglobulin that promotes NO synthesis. The absence of malpha2M, in alpha2M(-/-) mice, may allow TGF-beta to more efficiently suppress excessive iNOS expression following endotoxin challenge... - A modified human alpha 2-macroglobulin derivative that binds tumor necrosis factor-alpha and interleukin-1 beta with high affinity in vitro and reverses lipopolysaccharide toxicity in vivo in miceD J Webb
Department of Pathology, University of Virginia Health Sciences Center, Charlottesville 22908, USA
Lab Invest 78:939-48. 1998..Thus, MAC may have therapeutic potential in the control of chronic inflammatory disorders... - Characterization of the binding sites for plasminogen and tissue-type plasminogen activator in cytokeratin 8 and cytokeratin 18K R Kralovich
Department of Biochemistry and Molecular Genetics, University of Virginia Health Sciences Center, Charlottesville 22908, USA
J Protein Chem 17:845-54. 1998..These studies demonstrate that CK8 may promote plasminogen activation by t-PA only when present in an oligomerized state. CK18 may participate in the oligomer, together with CK8, based on its ability to bind t-PA... - Plasminogen binding to rat hepatocytes in primary culture and to thin slices of rat liverS L Gonias
Department of Pathology, University of Virginia Health Sciences Center, Charlottesville 22908
Blood 74:729-36. 1989..These studies suggest that hepatocyte plasminogen binding sites may provide important surface anticoagulant activity... - Interleukin-4 and IL-10 bind covalently to activated human alpha2-macroglobulin by a mechanism that requires Cys949T R Garber
Department of Pathology, University of Virginia Health Sciences Center, Charlottesville 22908, USA
J Interferon Cytokine Res 20:125-31. 2000..In these complexes, Cys949 is properly aligned to undergo thiol disulfide exchange and generate stable, covalent IL-4-alpha2M and IL-10-alpha2M complexes... - Myosin light chain kinase functions downstream of Ras/ERK to promote migration of urokinase-type plasminogen activator-stimulated cells in an integrin-selective mannerD H Nguyen
Department of Biochemistry and Molecular Genetics, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA
J Cell Biol 146:149-64. 1999..Thus, we have demonstrated that uPA promotes cellular migration, in an integrin-selective manner, by initiating a uPAR-dependent signaling cascade in which Ras, MEK, ERK, and MLCK serve as essential downstream effectors... - Low density lipoprotein receptor-related protein is expressed early and becomes restricted to a somatodendritic domain during neuronal differentiation in cultureM D Brown
Department of Pathology Neuropathology, University of Virginia Health Sciences Center, Charlottesville 22908, USA
Brain Res 747:313-7. 1997..These studies demonstrate that neuronal LRP undergoes selective compartmentation during neuronal maturation and suggest that LRP-mediated endocytosis is largely restricted to the somatodendritic compartment... - Covalent complexes of albumin with serotonin, ketanserin and lysergic acid antagonize the activity of serotonin in human plateletsS R VandenBerg
Department of Pathology, University of Virginia Health Sciences Center, Charlottesville 22908
Life Sci 44:1777-85. 1989..These prototypic 5-HT drug-protein conjugates may be useful for probing 5-HT2 receptor-ligand interactions in human platelets... - Reaction of nerve growth factor gamma and 7S nerve growth factor complex with human and murine alpha 2-macroglobulinB B Wolf
Department of Pathology, University of Virginia Health Sciences Center, Charlottesville 22908
Biochemistry 32:1875-82. 1993..This reaction may have depended exclusively on slow reversible dissociation of NGF-gamma from the 7S complex. NGF-gamma was rapidly inhibited by murine alpha 2M (m alpha 2M).(ABSTRACT TRUNCATED AT 250 WORDS).. - Transcriptional regulation of LDL receptor-related protein by IFN-gamma and the antagonistic activity of TGF-beta(1) in the RAW 264.7 macrophage-like cell lineI M Hussaini
Department of Pathology, University of Virginia Health Sciences Center, Charlottesville, 22908, USA
J Leukoc Biol 59:733-9. 1996..The studies presented here suggest that the balance between IFN-gamma and TGF-beta1 may be critical in determining LRP expression at sites of infection and inflammation... - Regulation of the composition of the extracellular matrix by low density lipoprotein receptor-related protein-1: activities based on regulation of mRNA expressionAlban Gaultier
Department of Pathology, School of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
J Biol Chem 281:7332-40. 2006..The ability of LRP-1 to regulate expression of the factors identified here suggests a role for LRP-1 in determining blood vessel structure and in angiogenesis... - Effects of low density lipoprotein receptor-related protein-1 on the expression of platelet-derived growth factor beta-receptor in vitroLihua Wu
Department of Pathology, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA
J Cell Biochem 93:1169-77. 2004..LRP-1 does not directly regulate PDGF beta-receptor phosphorylation or degradation in PDGF-BB-treated cells... - Low density lipoprotein receptor-related protein-1 promotes beta1 integrin maturation and transport to the cell surfaceAna Maria Salicioni
Department of Pathology, University of Virginia School of Medicine, Charlottesville 22908, USA
J Biol Chem 279:10005-12. 2004..These studies support a model in which LRP-1 either directly or indirectly promotes maturation of beta(1) integrin precursor and thereby increases the level of beta(1) integrin at the cell surface... - The low density lipoprotein receptor-related protein mediates fibronectin catabolism and inhibits fibronectin accumulation on cell surfacesAna M Salicioni
Department of Pathology, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA
J Biol Chem 277:16160-6. 2002..The function of LRP in Fn degradation and the ability of LRP to regulate levels of other plasma membrane proteins represent possible mechanisms whereby LRP prevents Fn accumulation on cell surfaces... - The low-density lipoprotein receptor-related protein-1 associates transiently with lipid raftsLihua Wu
Department of Pathology, University of California San Diego, La Jolla, California 92093, USA
J Cell Biochem 96:1021-33. 2005..Fluid movement of LRP-1 between microdomains may facilitate its function in promoting the endocytosis of other plasma membrane proteins, such as the urokinase receptor, which localizes in lipid rafts... - A shed form of LDL receptor-related protein-1 regulates peripheral nerve injury and neuropathic pain in rodentsAlban Gaultier
Department of Pathology, UCSD School of Medicine, La Jolla, California 92093 0629, USA
J Clin Invest 118:161-72. 2008..Our results show that sLRP-alpha is biologically active and may attenuate neuropathic pain. In the PNS, the function of LRP1 may reflect the integrated activities of the membrane-anchored and shed forms of LRP1... - The low-density lipoprotein receptor-related protein regulates cancer cell survival and metastasis developmentValerie Montel
Department of Pathology, University of California San Diego School of Medicine, La Jolla, California 92093 0612, USA
Cancer Res 67:9817-24. 2007..0% O2. These results suggest mechanisms by which LRP-1 may facilitate the development and growth of cancer metastases in vivo... - uPAR induces epithelial-mesenchymal transition in hypoxic breast cancer cellsRobin D Lester
Department of Pathology, University of California, San Diego, La Jolla, CA 92093, USA
J Cell Biol 178:425-36. 2007..We conclude that in hypoxia, uPAR activates diverse cell signaling pathways that cooperatively induce EMT and may promote cancer metastasis... - Low-density lipoprotein receptor-related protein 1 is an essential receptor for myelin phagocytosisAlban Gaultier
Department of Pathology, University of California, San Diego, La Jolla, CA 92093, USA
J Cell Sci 122:1155-62. 2009..LRP1 colocalized with multiple CNS cell types. These studies establish LRP1 as a major receptor for phagocytosis of degraded myelin, which may function alone or in concert with co-receptors previously implicated in myelin phagocytosis... - Ligand binding to LRP1 transactivates Trk receptors by a Src family kinase-dependent pathwayYang Shi
Department of Pathology, University of California San Diego, La Jolla, CA 92093 0612, USA
Sci Signal 2:ra18. 2009..Trk receptor transactivation provides a mechanism by which diverse LRP1 ligands may show neurotrophic activity... - Tissue-type plasminogen activator acts as a cytokine that triggers intracellular signal transduction and induces matrix metalloproteinase-9 gene expressionKebin Hu
Department of Pathology, University of Pittsburgh School of Medicine, S 405 Biomedical Science Tower, 200 Lothrop Street, Pittsburgh, PA 15261, USA
J Biol Chem 281:2120-7. 2006.... - Mutation of lysine 1370 in full-length human alpha2-macroglobulin blocks binding to the low density lipoprotein receptor-related protein-1Sanja Arandjelovic
Department of Pathology, University of California San Diego, 9500 Gilman Road, La Jolla, CA 92093 0612, USA
Arch Biochem Biophys 438:29-35. 2005..7 cells was blocked by receptor-associated protein, indicating an essential role for LRP-1. These studies demonstrate that a single mutation in full-length r(alpha)2M is sufficient to block binding to LRP-1... - Regulation of Rac1 activation by the low density lipoprotein receptor-related proteinZhong Ma
Department of Pathology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA
J Cell Biol 159:1061-70. 2002..In uPAR-negative cells, LRP-1 neutralization does not affect Rac1 activation, and other mechanisms by which LRP-1 may regulate cell migration are not unmasked... - Distinct binding sites in the structure of alpha 2-macroglobulin mediate the interaction with beta-amyloid peptide and growth factorsJoseph M Mettenburg
Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA
J Biol Chem 277:13338-45. 2002..These studies suggest a model in which alpha(2)M has three protein interaction sites with distinct specificities, mediating the interaction with Abeta, growth factors, and LRP... - Molecular dissection of the human alpha2-macroglobulin subunit reveals domains with antagonistic activities in cell signalingElisabetta Mantuano
Department of Pathology and Anesthesiology, University of California San Diego, La Jolla, CA 92093, USA
J Biol Chem 283:19904-11. 2008.... - Functional analysis of plasma alpha(2)-macroglobulin from Alzheimer's disease patients with the A2M intronic deletionCaroline Hope
Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA
Neurobiol Dis 14:504-12. 2003..These observations suggest a possible functional basis by which the A2M deletion may influence multifactorial AD pathogenesis... - Beta-amyloid peptide binds equivalently to binary and ternary alpha2-macroglobulin-protease complexesJoseph M Mettenburg
Department of Biochemistry and Molecular Genetics University of Virginia School of Medicine, Charlottesville, Virginia, 22908, USA
Protein J 24:89-93. 2005..The TGF-beta- and Abeta-binding sites are spatially separated not only in the primary sequence of alpha2M, but also in the 3D-structure... - Limited mutations in full-length tetrameric human alpha2-macroglobulin abrogate binding of platelet-derived growth factor-BB and transforming growth factor-beta1Sanja Arandjelovic
Department of Pathology, University of California San Diego, La Jolla, California 92093, USA
J Biol Chem 281:17061-8. 2006..The exact sequences required for binding different growth factors may be non-identical, mimicking the model of the bait region in which different proteases target adjacent and sometimes overlapping sequences... - A chemically modified preparation of alpha2-macroglobulin binds beta-amyloid peptide with increased affinity and inhibits Abeta cytotoxicityJoseph M Mettenburg
Department of Pathology, University of California, San Diego, La Jolla, California, USA
J Neurochem 93:53-62. 2005..We propose that alpha2M-cis-Pt/MA is a novel alternative to Abeta-specific antibodies, for studying the efficacy of Abeta-binding agents in vitro and in vivo... - Growth factor-binding sequence in human alpha2-macroglobulin targets the receptor-binding site in transforming growth factor-betaSanja Arandjelovic
Department of Biochemistry and Molecular Genetics, Box 800214, Charlottesville, Virginia 22908, USA
Biochemistry 42:6121-7. 2003..The same peptides also inhibited the activity of TGF-beta1 in endothelial cell proliferation assays. These results demonstrate that alpha(2)M-derived peptides target the receptor-binding sequence in TGF-beta... - Binding of alpha2ML1 to the low density lipoprotein receptor-related protein 1 (LRP1) reveals a new role for LRP1 in the human epidermisMarie Florence Galliano
UMR5165 UDEAR CNRS UPS, CHU Purpan, Toulouse, France
PLoS ONE 3:e2729. 2008..The expression of LRP1 in epidermis as well as its ability to internalize alpha2ML1 was investigated... - Epidermal growth factor receptor-dependent and -independent cell-signaling pathways originating from the urokinase receptorMinji Jo
Department of Pathology, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA
J Biol Chem 278:1642-6. 2003..We conclude that the EGFR may function as a transducer of the signal from uPAR to ERK, but not Rac1. In the absence of EGFR, an alternative pathway links uPAR to ERK; however, this pathway is apparently silenced by EGFR expression... - High-resolution imaging of the dynamic tumor cell vascular interface in transparent zebrafishKonstantin Stoletov
Department of Pathology and Moores Cancer Center, University of California at San Diego, 9500 Gilman Drive, MC0612, La Jolla, CA 92093, USA
Proc Natl Acad Sci U S A 104:17406-11. 2007..Zebrafish could also provide a cost-effective means for the rapid development of therapeutic agents directed at blocking human cancer progression and tumor-induced angiogenesis... - Autoantibodies in canine masticatory muscle myositis recognize a novel myosin binding protein-C family memberXiaohua Wu
Department of Pathology, University of California, San Diego 92101, USA
J Immunol 179:4939-44. 2007..Understanding the role of mMyBP-C in this canine inflammatory myopathy may advance our knowledge of mechanisms of autoimmune inflammatory muscle diseases, not only in dogs, but also in humans... - A derivative of the plasma protease inhibitor alpha(2)-macroglobulin regulates the response to peripheral nerve injurySanja Arandjelovic
Department of Pathology, University of California, San Diego School of Medicine, La Jolla, California 92093, USA
J Neurochem 103:694-705. 2007..These studies demonstrate that an alpha2M derivative is capable of regulating the response to peripheral nerve injury by a mechanism that requires low-density lipoprotein receptor-related protein-1... - Dynamic assembly of the urokinase-type plasminogen activator signaling receptor complex determines the mitogenic activity of urokinase-type plasminogen activatorMinji Jo
Department of Pathology, University of California San Diego School of Medicine, La Jolla, California 92093, USA
J Biol Chem 280:17449-57. 2005..We conclude that expression and assembly of uPAR co-receptors in a specific cell type determines the response to uPA. The EGFR selectively cooperates with uPAR to mediate mitogenesis... - Activation of hepatocyte growth factor by urokinase-type plasminogen activator is ionic strength-dependentWendy M Mars
Department of Pathology, University of Pittsburgh, S411 B Biomedical Science Tower, Pittsburgh, PA 15261, USA
Biochem J 390:311-5. 2005..These results support a model in which the ability of u-PA to activate scHGF in vivo may be highly dependent on local conditions within the extracellular space... - Cooperativity between the Ras-ERK and Rho-Rho kinase pathways in urokinase-type plasminogen activator-stimulated cell migrationMinji Jo
Department of Pathology, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA
J Biol Chem 277:12479-85. 2002..This study supports a model in which the Ras-ERK and Rho-Rho kinase pathways cooperate to promote cell migration. Neutralizing either pathway is sufficient to block the response to agents that stimulate cell migration by activating ERK...