Linked Life Data

2318860

Source:http://linkedlifedata.com/resource/pubmed/id/2318860

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
1990-5-10
pubmed:abstractText
The precursor for transforming growth factor-alpha (TGF-alpha) is a membrane glycoprotein that can establish contact with epidermal growth factor/TGF-alpha receptors on adjacent cells or can be cleaved to release TGF-alpha that diffuses into the medium. Cleavage of pro-TGF-alpha occurs at Ala/Leu-Ala/Leu-Ala-Val-Val sites located at each end of the mature TGF-alpha sequence. To characterize the cleavage process of pro-TGF-alpha and the role of glycosylation in this process, we have introduced a pro-TGF-alpha expression vector in wild type Chinese hamster ovary (CHO) cells and in the mutant CHO cell clone ldlD that has a reversible defect in protein glycosylation. Analysis of metabolically labeled and cell surface-labeled products immunoprecipitated with antibodies directed against the extracellular TGF-alpha sequence and the cytoplasmic pro-TGF-alpha C-terminal domain shows that cleavage of pro-TGF-alpha in wild type CHO cells occurs in two steps. Both processing steps occur after pro-TGF-alpha reaches the cell surface. In the first step, pro-TGF-alpha rapidly (t1/2 = 30 min) loses the amino-terminal segment that precedes the TGF-alpha sequence. In the second step, pro-TGF-alpha is cleaved at the carboxyl terminus of the TGF-alpha sequence releasing this factor into the medium. This second step is slow (t1/2 = 2 h). The action of pancreatic elastase added to CHO-TGF-alpha cells mimics the first step but not the second one. Synthesis, cell surface exposure, rate of cleavage, and generation of bioactive TGF-alpha in ldlD-TGF-alpha cells are not markedly affected by the lack of N-acetylgalactosamine-dependent protein O-glycosylation or galactose-dependent glycan chain modification. The results indicate that, despite their similarity in amino acid sequence, the two cleavage sites that flank TGF-alpha may be processed with different kinetics which can lead to retention of pro-TGF-alpha on the cell surface.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
265
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6410-5
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:2318860-Amino Acid Sequence, pubmed-meshheading:2318860-Animals, pubmed-meshheading:2318860-Cell Line, pubmed-meshheading:2318860-Cell Membrane, pubmed-meshheading:2318860-Cysteine, pubmed-meshheading:2318860-Genetic Vectors, pubmed-meshheading:2318860-Glycosylation, pubmed-meshheading:2318860-Growth Substances, pubmed-meshheading:2318860-Kinetics, pubmed-meshheading:2318860-Molecular Sequence Data, pubmed-meshheading:2318860-Plasmids, pubmed-meshheading:2318860-Protein Precursors, pubmed-meshheading:2318860-Protein Processing, Post-Translational, pubmed-meshheading:2318860-Rats, pubmed-meshheading:2318860-Sulfur Radioisotopes, pubmed-meshheading:2318860-Transfection, pubmed-meshheading:2318860-Transforming Growth Factor alpha, pubmed-meshheading:2318860-Transforming Growth Factors
pubmed:year
1990
pubmed:articleTitle
Generation of transforming growth factor-alpha from the cell surface by an O-glycosylation-independent multistep process.
pubmed:affiliation
Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't