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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
|
| pubmed:dateCreated |
1996-11-22
|
| pubmed:abstractText |
The phosphorylation of insulin-like growth factor binding protein-I (IGFBP-1) alters its binding affinity for insulin-like growth factor I (IGF-I) and thus regulates the bioavailability of IGF-I for binding to the IGF-I receptor. The kinase(s) responsible for the phosphorylation of IGFBP-1 has not been identified. This study was designed to characterize the IGFBP-1 kinase activity in HepG2 human hepatoma cells, a cell line that secretes IGFBP-1 primarily as phosphorylated isoforms. IGFBP-1 kinase activity was partially purified from detergent extracts of the cells by phosphocellulose chromatography and gel filtration. Two kinases of approximate M(r) 150,000 (peak I kinase) and M(r) 50,000 (peak II kinase) were identified. Each kinase phosphorylated IGFBP-1 at serine residues that were phosphorylated by intact HepG2 cells. The kinases were distinct based on their differential sensitivity to inhibition by heparin (IC50 = 2.5 and 16.5 micrograms/ml, peak I and II kinase, respectively) and inhibition by the isoquinoline sulfonamide CKI-7 (IC50 = 50 microM and 100 microM, peak I and II kinase, respectively). In addition, a tenfold molar excess of nonradioactive GTP relative to [gamma-32P]ATP lowered the incorporation of 32P into IGFBP-1 by 80% when the reaction was catalyzed by the peak I kinase, whereas GTP had no effect on the reaction catalyzed by the peak II kinase. In the presence of polylysine, IGFBP-1 was radiolabeled by the partially purified kinase activity when [gamma-32P]GTP served as the phosphate donor indicating the presence of casein kinase II activity. Furthermore, IGFBP-1 was phosphorylated by purified casein kinase I and casein kinase II at sites phosphorylated by the peak I and II kinases. Our data suggest that at least two kinases could be responsible for the phosphorylation of IGFBP-1 in intact HepG2 cells and that the kinases are related to the casein kinase family of protein kinases.
|
| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Casein Kinase II,
http://linkedlifedata.com/resource/pubmed/chemical/Casein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Guanosine Triphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Heparin,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin-Like Growth Factor Binding...,
http://linkedlifedata.com/resource/pubmed/chemical/Isoquinolines,
http://linkedlifedata.com/resource/pubmed/chemical/N-(2-aminoethyl)-5-chloroisoquinolin...,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoserine,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Mar
|
| pubmed:issn |
0730-2312
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
1
|
| pubmed:volume |
60
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
387-99
|
| pubmed:dateRevised |
2009-11-19
|
| pubmed:meshHeading |
pubmed-meshheading:8867814-Amino Acid Sequence,
pubmed-meshheading:8867814-Carcinoma, Hepatocellular,
pubmed-meshheading:8867814-Casein Kinase II,
pubmed-meshheading:8867814-Casein Kinases,
pubmed-meshheading:8867814-Enzyme Inhibitors,
pubmed-meshheading:8867814-Guanosine Triphosphate,
pubmed-meshheading:8867814-Heparin,
pubmed-meshheading:8867814-Humans,
pubmed-meshheading:8867814-Insulin-Like Growth Factor Binding Protein 1,
pubmed-meshheading:8867814-Isoquinolines,
pubmed-meshheading:8867814-Liver Neoplasms,
pubmed-meshheading:8867814-Molecular Sequence Data,
pubmed-meshheading:8867814-Molecular Weight,
pubmed-meshheading:8867814-Peptide Mapping,
pubmed-meshheading:8867814-Phosphorylation,
pubmed-meshheading:8867814-Phosphoserine,
pubmed-meshheading:8867814-Protein Kinases,
pubmed-meshheading:8867814-Protein-Serine-Threonine Kinases,
pubmed-meshheading:8867814-Tumor Cells, Cultured
|
| pubmed:year |
1996
|
| pubmed:articleTitle |
Characterization of insulin-like growth factor binding protein-1 kinases from human hepatoma cells.
|
| pubmed:affiliation |
Department of Medicine, University of North Carolina, Chapel Hill 27599, USA.
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
|