Lack of L-iduronic acid in heparan sulfate affects interaction with growth factors and cell signaling.

ABSTRACT: HSEPI (glucuronyl C5-epimerase) catalyzes the conversion of d-glucuronic acid to l-iduronic acid in heparan sulfate (HS) biosynthesis. Disruption of the Hsepi gene in mice yielded a lethal phenotype with selective organ defects but had remarkably little effect on other organ systems. We have approached the underlying mechanisms by examining the course and effects of FGF2 signaling in a mouse embryonic fibroblast (MEF) cell line derived from the Hsepi(-)(/)(-) mouse. The HS produced by these cells is devoid of l-iduronic acid residues but shows up-regulated N- and 6-O-sulfation compared with wild type (WT) MEF HS. In medium fortified with 10% fetal calf serum, the Hsepi(-)(/)(-) MEFs proliferated and migrated similarly to WT cells. Under starvation conditions, both cell types showed attenua

SUBMITTER: Jia J 

PROVIDER: S-EPMC2708889 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature