Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P39060 (
endostatin
)
2,284
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Endostatin, the C-terminal fragment of
collagen XVIII
, is a potent inhibitor of angiogenesis. Observations that
endostatin
inhibits endothelial cell migration and induces disassembly of the actin cytoskeleton provide putative cellular mechanisms for this effect. To understand the mechanisms of
endostatin
-induced intracellular signaling, we analyzed the association of recombinant
endostatin
with endothelial cell lipid rafts and the roles of its heparin- and integrin-binding properties in this interaction. We observed that a fraction of cell surface-bound
endostatin
partitioned in low density membrane raft fractions together with caveolin-1. Heparinase treatment of cells prevented the recruitment of
endostatin
to the lipid rafts but did not affect the association of
endostatin
with the non-raft fraction, whereas preincubation of
endostatin
with soluble alpha5beta1 integrin prevented the association of
endostatin
with the endothelial cell membrane. Endostatin treatment induced recruitment of alpha5beta1 integrin into the raft fraction via a heparan sulfate proteoglycan-dependent mechanism. Subsequently, through alpha5beta1 integrin, heparan sulfate, and lipid raft-mediated interactions,
endostatin
induced Src-dependent activation of
p190RhoGAP
with concomitant decrease in RhoA activity and disassembly of actin stress fibers and focal adhesions. These observations provide a cell biological mechanism, which plausibly explains the anti-angiogenic mechanisms of
endostatin
in vivo.
...
PMID:Endostatin associates with lipid rafts and induces reorganization of the actin cytoskeleton via down-regulation of RhoA activity. 1285 10
