Linked Life Data

9724028

Source:http://linkedlifedata.com/resource/pubmed/id/9724028

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
1998-9-23
pubmed:abstractText
To investigate endoproteolytic processing of the type I insulin-like growth factor receptor (IGF-IR), we have examined its structure and activity in the furin-deficient LoVo-C5 cell line. Immunoprecipitation experiments using the monoclonal anti-IGF-IR antibody (alpha-IR3) showed that LoVo-C5 cells expressed a major high molecular mass receptor (200 kDa) corresponding to the unprocessed alpha/beta pro-receptor. A small amount of successfully cleaved alpha/beta heterodimers was also produced, indicating a residual endoproteolytic cleavage activity in these cells. In vitro, a soluble form of recombinant furin was able to cleave the pro-IGF-IR (200 kDa) into alpha-subunit (130 kDa) and beta-subunit (97 kDa). Measurement of IGF binding parameters in LoVo-C5 cells indicated a low number of typical type I IGF-binding sites (binding capacity, 5 x 10(3) sites/cell; Kd, 1.9 nM for IGF-I and 7.0 nM for IGF-II). These findings in LoVo-C5 contrast with those in HT29-D4 cells, which have active furin, and where IGF-IR (2.8 x 10(4) sites/cell) was fully processed. Moreover, the 200-kDa pro-IGF-IR of LoVo-C5 was unable to induce intracellular signaling, such as beta-subunit tyrosine autophosphorylation and insulin-related substrate-1 tyrosine phosphorylation. Flow immunocytometry analysis using alpha-IR3 antibody indicated that LoVo-C5 cells expressed 40% more receptors than HT29-D4 cells, suggesting that in LoVo-C5 cells only the small amount of mature type I IGF-IR binds IGFs with high affinity. To provide evidence for this idea, we showed that mild trypsin treatment of living LoVo-C5 cells partially restored alpha/beta cleavage of IGF-IR, and greatly enhanced (6-fold) the IGF-I binding capacity of LoVo-C5 cells, but did not restore IGF-IR signaling activity. Moreover, LoVo-C5 cells were totally unresponsive to IGF-I in terms of cell migration, in contrast to fully processed IGF-IR-HT29-D4 cells. Our data indicate that furin is involved in the endoproteolytic processing of the IGF-IR and suggest that this posttranslational event might be crucial for its ligand binding and signaling activities. However, our data do not exclude that other proprotein convertases could participate to IGF-IR maturation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0013-7227
pubmed:author
pubmed:issnType
Print
pubmed:volume
139
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3763-71
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:9724028-ADP Ribose Transferases, pubmed-meshheading:9724028-Bacterial Toxins, pubmed-meshheading:9724028-Cell Movement, pubmed-meshheading:9724028-Drug Resistance, pubmed-meshheading:9724028-Exotoxins, pubmed-meshheading:9724028-Flow Cytometry, pubmed-meshheading:9724028-Furin, pubmed-meshheading:9724028-Humans, pubmed-meshheading:9724028-Insulin-Like Growth Factor I, pubmed-meshheading:9724028-Phosphorylation, pubmed-meshheading:9724028-Protein Processing, Post-Translational, pubmed-meshheading:9724028-Receptors, Somatomedin, pubmed-meshheading:9724028-Signal Transduction, pubmed-meshheading:9724028-Subtilisins, pubmed-meshheading:9724028-Trypsin, pubmed-meshheading:9724028-Tumor Cells, Cultured, pubmed-meshheading:9724028-Tyrosine, pubmed-meshheading:9724028-Virulence Factors
pubmed:year
1998
pubmed:articleTitle
Deficient processing and activity of type I insulin-like growth factor receptor in the furin-deficient LoVo-C5 cells.
pubmed:affiliation
Unité Interactions entre Systèmes Protéiques et Différenciation dans la Cellule Tumorale, UPRES-A CNRS 6032, Université d'Aix-Marseille I, Faculté de Pharmacie, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't