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Your search keyword '"Vlodavsky, Israel"' showing total 27 results
Start Over Author "Vlodavsky, Israel" Journal journal of biological chemistry
27 results on '"Vlodavsky, Israel"'

10. Heparanase Enhances Syndecan-1 Shedding

Author

Yang, Yang, primary, MacLeod, Veronica, additional, Miao, Hua-Quan, additional, Theus, Allison, additional, Zhan, Fenghuang, additional, Shaughnessy, John D., additional, Sawyer, Jeffrey, additional, Li, Jin-Ping, additional, Zcharia, Eyal, additional, Vlodavsky, Israel, additional, and Sanderson, Ralph D., additional

Published
2007
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25. Phosphorothioate Oligodeoxynucleotides Bind to Basic Fibroblast Growth Factor, Inhibit Its Binding to Cell Surface Receptors, and Remove It from Low Affinity Binding Sites on Extracellular Matrix (∗)

Author

Guvakova, Marina A., Yakubov, Leonid A., Vlodavsky, Israel, Tonkinson, John L., and Stein, C.A.

Abstract

We studied the interactions of phosphorothioate oligodeoxynucleotides and heparin-binding growth factors. By means of a gel mobility shift assay, we demonstrated that phosphodiester and phosphorothioate homopolymers bound to basic fibroblast growth factor (bFGF). Binding of a probe phosphodiester oligodeoxynucleotide could also be shown for other proteins of the FGF family, including acidic fibroblast growth factor (aFGF), Kaposi's growth factor (FGF-4) as well as for the bFGF-related vascular endothelial growth factor, VEGF. No binding to epidermal growth factor (EGF) was observed. In addition, using a radioreceptor assay, we have shown that phosphorothioate homopolymers of cytidine and thymidine blocked binding of not only 125I-bFGF, but also of 125I-PDGF to NIH 3T3 cells, whereas phosphodiester oligodeoxynucleotides were ineffective. The extent of blockade of binding was dependent on the chain length of the phosphorothioate oligodeoxynucleotide. Furthermore, we have examined the effects of 18-mer phosphorothioate oligodeoxynucleotides of different sequences on 125I-bFGF binding to low and high affinity sites on both NIH 3T3 fibroblasts and DU-145 prostate cancer cells. Despite the fact that we have observed inhibition of bFGF binding by the 18-mer phosphorothioate oligodeoxynucleotides for both the high and low affinity classes of bFGF receptor, the inhibition was sequence-selective only for the high affinity receptors. We have also demonstrated that phosphorothioate homopolymers of cytidine and thymidine release bFGF bound to low affinity receptors in extracellular matrix (ECM). Finally, the most potent phosphorothioate oligodeoxynucleotides used in these experiments (e.g.SdC28) were inhibitors of bFGF-induced DNA synthesis in NIH 3T3 cells.

Published
1995
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26. Characterization of Heparanase-induced Phosphatidylinositol a3-Kinase-AKT Activation and Its Integrin Dependence.

Author

Riaz, Anjum, Ilan, Neta, Vlodavsky, Israel, Jin-Ping Li, and Johansson, Staffan

Subjects
*HEPARANASE, *PHOSPHATIDYLINOSITOL 3-kinases, *INTEGRINS, *PHOSPHORYLATION, *BIOCHEMISTRY
Abstract

Heparanase functions as a heparan sulfate-degrading enzyme and as a ligand for an unidentified signaling receptor(s). Here, several reactions involved in the activation of the PI3K-AKT pathway by latent heparanase were characterized. Protein suppression using specific siRNAs revealed that heparanase-induced phosphorylation of AKT at Ser-473 was RICTOR-mTOR-dependent, whereas ILK and PAK1/2 were dispensable. p110α was the PI3K catalytic isoform preferred by heparanase for AKT activation and cell proliferation because the p110α inhibitor YM024 blocked these processes. Heparanase-induced AKT phosphorylation was low in mouse embryonic fibroblast cells expressing a RAS interaction-defective p110α compared with wild type cells, indicating that RAS has an important role in the PI3K-AKT activation. The response to heparanase was also inefficient in suspension cultures of several cell lines, suggesting a requirement of integrins in this pathway. Adhesion via either αVβ3 or α5β1 promoted heparanase-induced AKT phosphorylation, and a stronger effect was seen when both integrins were engaged. Simultaneous inhibition of FAK and PYK2 using a chemical inhibitor, or suppression of their expression, inhibited heparanase-induced AKT activation and cell proliferation. Stimulation of cells with heparanase enhanced their resistance against oxidative stress- or growth factor starvation-induced apoptosis. These results demonstrate that there is an intimate cross-talk between the heparanase receptor(s) and integrins during induction of the prosurvival PI3K-AKT pathway by heparanase. [ABSTRACT FROM AUTHOR]

Published
2013
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27. Processing of Macromolecular Heparin by Heparanase.

Author

Feng Gong, Per Jemth, Galvis, Martha L. Escobar, Vlodavsky, Israel, Horner, Alan, Lindahl, Ulf, and Jin-ping Li

Subjects
*HEPARIN, *PROTEOGLYCANS, *POLYSACCHARIDES
Abstract

Heparanase is an endo-glucuronidase expressed in a variety of tissues and cells that selectively cleaves extracellular and cell-surface heparan sulfate. Here we propose that this enzyme is involved also in the processing of serglycin heparin proteoglycan in mouse mast cells. In this process, newly synthesized heparin chains (60-100 kDa) are degraded to fragments (10-20 kDa) similar in size to commercially available heparin (Jacobsson, K. G., and Lindahl, U. (1987) Biochem. J. 246, 409-415). A fraction of these fragments contains the specific pentasaccharide sequence required for high affinity binding to antithrombin implicated with anticoagulant activity. Rat skin heparin, which escapes processing in vivo, was used as a substrate in reaction with recombinant human heparanase. An incubation product of commercial heparin size retained the specific pentasaccharide sequence, although oligosaccharides (3-4 kDa) containing this sequence could be degraded by the same enzyme. Commercial heparin was found to be a powerful inhibitor (I[sub 50] ∼20 nM expressed as disaccharide unit, ∼0.7 nM polysaccharide) of heparanase action toward antithrombin-binding oligosaccharides. Cells derived from a serglycin-processing mouse mastocytoma expressed a protein highly similar to other mammalian heparanases. These findings strongly suggest that the intracellular processing of the heparin proteoglycan polysaccharide chains is catalyzed by heparanase, which primarily cleaves target structures distinct from the antithrombin-binding sequence. [ABSTRACT FROM AUTHOR]

Published
2003
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