Linked Life Data

19877579

Source:http://linkedlifedata.com/resource/pubmed/id/19877579

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
49
pubmed:dateCreated
2009-12-8
pubmed:abstractText
Endostatin is a potent angiogenesis inhibitor with heparin-dependent activities. Nucleolin, a novel functional receptor of endostatin, mediates both the internalization to endothelial cells and the antiangiogenic activity of endostatin. To define the exact role of the heparin binding motif in mediating the interaction between endostatin and its receptor nucleolin, up to six arginine residues (R155, R158, R184, R270, R193, and R194) located in the heparin binding motif of endostatin were substituted by alanine to make double, quadruple, or hexad point mutations, respectively. Contributions of the heparin binding motif to both the interaction with nucleolin and the biological activities of endostatin were investigated from in vitro to in vivo. Here we show that Arg to Ala point mutagenesis of the heparin binding motif does not interrupt the folding of endostatin but significantly impairs the interaction between endostatin and nucleolin. Double and quadruple mutants showed significantly decreased internalization to endothelial cells and antitumor activities, while the hexad Arg to Ala mutant completely lost its interaction with nucleolin and biological functions. Taken together, the present study demonstrates that the arginine clusters in the heparin binding motif of endostatin significantly contribute to its interaction with receptor nucleolin and mediate the antiangiogenic and antitumor activities of endostatin.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1520-4995
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
48
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
11655-63
pubmed:meshHeading
pubmed-meshheading:19877579-Alanine, pubmed-meshheading:19877579-Amino Acid Motifs, pubmed-meshheading:19877579-Amino Acid Substitution, pubmed-meshheading:19877579-Angiogenesis Inhibitors, pubmed-meshheading:19877579-Animals, pubmed-meshheading:19877579-Antineoplastic Agents, pubmed-meshheading:19877579-Arginine, pubmed-meshheading:19877579-Cell Line, Tumor, pubmed-meshheading:19877579-Endostatins, pubmed-meshheading:19877579-Heparin, pubmed-meshheading:19877579-Humans, pubmed-meshheading:19877579-Mice, pubmed-meshheading:19877579-Mice, Inbred C57BL, pubmed-meshheading:19877579-Mutagenesis, Site-Directed, pubmed-meshheading:19877579-Phosphoproteins, pubmed-meshheading:19877579-Point Mutation, pubmed-meshheading:19877579-Protein Binding, pubmed-meshheading:19877579-Protein Conformation, pubmed-meshheading:19877579-RNA-Binding Proteins
pubmed:year
2009
pubmed:articleTitle
The heparin binding motif of endostatin mediates its interaction with receptor nucleolin.
pubmed:affiliation
National Engineering Laboratory for Anti-tumor Protein Therapeutics, Tsinghua University, Beijing 100084, PR China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't