Heparanase Induces Akt Phosphorylation Via a Lipid Raft Receptor

Overview

Journal Biochem Biophys Res Commun

Publisher Elsevier

Specialty Biochemistry

Date 2007 Aug 11

PMID 17689495

Citations 27

Authors

Olga Ben-Zaken

Svetlana Gingis-Velitski

Israel Vlodavsky

Neta Ilan

Affiliations

Soon will be listed here.

Abstract

The endoglycosidase heparanase is the predominant enzyme that degrades heparan sulfate side chains of heparan sulfate proteoglycans, activity that is strongly implicated in tumor metastasis. Apart of its well characterized enzymatic activity, heparanase was noted to exert also enzymatic-independent functions. Among these is the induction of Akt/PKB phosphorylation noted in endothelial- and tumor-derived cells. Protein domains of heparanase required for signaling were not identified to date, nor were identified heparanase binding proteins/receptors capable of transmitting heparanase signals. Here, we examined the possible function of mannose 6-phosphate receptor (MPR) and low-density lipoprotein-receptor related protein (LRP), recently implicated in cellular uptake of heparanase, as heparanase receptors mediating Akt phosphorylation. We found that heparanase addition to MPR- and LRP-deficient fibroblasts elicited Akt activation indistinguishable from control fibroblasts. In contrast, disruption of lipid rafts abrogated Akt/PKB phosphorylation following heparanase addition. These results suggest that lipid raft-resident receptor mediates heparanase signaling.

Citing Articles

The Heparanase Regulatory Network in Health and Disease.

Mayfosh A, Nguyen T, Hulett M Int J Mol Sci. 2021; 22(20).

PMID: 34681753 PMC: 8541136. DOI: 10.3390/ijms222011096.

Biology of the Heparanase-Heparan Sulfate Axis and Its Role in Disease Pathogenesis.

Vlodavsky I, Barash U, Nguyen H, Yang S, Ilan N Semin Thromb Hemost. 2021; 47(3):240-253.

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Rafting Down the Metastatic Cascade: The Role of Lipid Rafts in Cancer Metastasis, Cell Death, and Clinical Outcomes.

Greenlee J, Subramanian T, Liu K, King M Cancer Res. 2020; 81(1):5-17.

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Membrane Cholesterol Is Crucial for Surface Layer Protein Binding and Triggering Inflammasome Activation.

Chen Y, Huang K, Chen L, Wu H, Hsu C, Tsai Y Front Immunol. 2020; 11:1675.

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Heparanase, cell signaling, and viral infections.

Koganti R, Suryawanshi R, Shukla D Cell Mol Life Sci. 2020; 77(24):5059-5077.

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