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Suramin modulates cellular levels of hepatocyte growth factor receptor by inducing shedding of a soluble form.

Abstract：

:Several growth factor receptors undergo shedding from the cell surface as a result of limited proteolysis via mechanisms that are at present poorly understood. By Western blotting of the conditioned media and cell lysates of several cell lines expressing the hepatocyte growth factor receptor, we found that suramin, a pharmacological agent that inhibits the activity of many growth factors, was able to induce shedding of this receptor. Increased levels of soluble hepatocyte growth factor receptor were observed in the conditioned media of GTL-16, a cell line over-expressing the receptor, as early as ten minutes after initial exposure to the agent, and incubation of this line with 300 microM suramin caused a 50% reduction in cell-associated levels of receptor after 6 hours. Although protein kinase C activation by treatment of cells with phorbol esters has previously been found to stimulate shedding of the hepatocyte growth factor receptor, this hitherto undescribed activity of suramin was not affected by protein kinase C inhibitors. Since shedding represents a possible means of down-modulation of receptor activity, suramin may inhibit the hepatocyte growth factor ligand/receptor system, not only by abrogation of hepatocyte growth factor binding to intact receptor, but also by induction of receptor shedding.

journal_name

Biochem Pharmacol

journal_title

Biochemical pharmacology

authors

Galvani AP,Cristiani C,Carpinelli P,Landonio A,Bertolero F

doi

10.1016/0006-2952(95)00219-p

subject

Has Abstract

pub_date

1995-09-28 00:00:00

pages

959-66

issue

7

eissn

0006-2952

issn

1873-2968

pii

0006-2952(95)00219-P

journal_volume

50

pub_type

杂志文章

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