Linked Life Data

12861049

Source:http://linkedlifedata.com/resource/pubmed/id/12861049

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2003-7-15
pubmed:abstractText
The interleukin-10 (IL-10) activation of Janus kinase (JAK) family members (JAK1/TYK2) and IL-10E1 is subsequently inactivated by approximately 3-4 h in primary prostate tumor lines. We examined the effect of proteasome inhibition on IL-10 activation of the IL-10E1 pathway following stimulation of HPCA-10a cells. Treatment of HPCA-10a cells with the proteasome inhibitor, N-acetyl-L-leucinyl-L-leucinyl-norleucinal (LLnL), led to stable tyrosine phosphorylation of the IL-10 receptor and IL-10E1 following stimulation. Further investigation showed that these stable phosphorylation events were the result of prolonged activation of JAK1 and TYK2 plus IL-10E1. IL-10E1 signaling normally induced the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) and LLnL treatment of the HPCA-10a and HPCA-10c cells significantly enhanced IL-10 induction of TIMP-1 levels to block tumor cell invasion in modified Boyden chamber invasion assays. These observations were confirmed using pharmacologic inhibitors by Western blot and ELISAs. In the presence of LLnL, stable phosphorylation of IL-10E1 and induction of TIMP-1 was abrogated if the tyrosine kinase inhibitor, staurosporine, was added. The effect of staurosporine on IL-10E1 phosphorylation and TIMP-1 could be overcome if the phosphatase inhibitor, vanadate, was also added, suggesting that phosphorylated IL-10E1 could be stabilized by phosphatase, but not by proteasome inhibition. These observations are consistent with the hypothesis that proteasome-mediated protein degradation can modulate the activity of the IL-10E1 pathway and TIMP-1 induction by regulating the deactivation of JAK1/TYK2.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1541-7786
pubmed:author
pubmed:issnType
Print
pubmed:volume
1
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
631-42
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:12861049-Antibodies, pubmed-meshheading:12861049-Cell Line, Tumor, pubmed-meshheading:12861049-Electrophoretic Mobility Shift Assay, pubmed-meshheading:12861049-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:12861049-Gene Expression Regulation, pubmed-meshheading:12861049-Humans, pubmed-meshheading:12861049-Interleukin-10, pubmed-meshheading:12861049-Leupeptins, pubmed-meshheading:12861049-Male, pubmed-meshheading:12861049-Phosphorylation, pubmed-meshheading:12861049-Phosphotyrosine, pubmed-meshheading:12861049-Prostatic Neoplasms, pubmed-meshheading:12861049-Protease Inhibitors, pubmed-meshheading:12861049-Proto-Oncogene Proteins c-rel, pubmed-meshheading:12861049-Signal Transduction, pubmed-meshheading:12861049-Staurosporine, pubmed-meshheading:12861049-Tissue Inhibitor of Metalloproteinase-1
pubmed:year
2003
pubmed:articleTitle
Interleukin-10 activation of the interleukin-10E1 pathway and tissue inhibitor of metalloproteinase-1 expression is enhanced by proteasome inhibitors in primary prostate tumor lines.
pubmed:affiliation
Department of Pathology and Laboratory Medicine, College of Medicine, Drexel University, Philadelphia, PA 19102-1192, USA. stearnsm1@aol.com
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.