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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
42
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pubmed:dateCreated |
2002-10-15
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pubmed:abstractText |
Transforming growth factor-beta1 (TGF-beta1) is a multipotential cytokine, which regulates remodeling of tissue extracellular matrix during early tumorigenesis and wound healing. Human enhancer of filamentation-1 (HEF1), a multifunctional docking protein, is involved in integrin-based signaling, which affects cell motility, growth, and apoptosis. Our studies reveal that TGF-beta1 is a potent inducer of HEF1 gene transcription in human dermal fibroblasts. TGF-beta1 promoted HEF1 expression in a dose-dependent manner and resulted in a 16-fold increase in HEF1 protein level. TGF-beta1 had no effect on the stability of either HEF1 protein or mRNA. The TGF-beta1-induced HEF1 expression was independent of cell adhesion and resistant to cytoskeleton disruption. TGF-beta1 increased levels of both p105 and p115 HEF1 in adherent fibroblasts. Digestion with specific phosphatases indicated that the p115HEF1 resulted from serine/threonine phosphorylation of p105HEF1. The appearance of the p115HEF1 as well as tyrosine phosphorylation of p105HEF1 required cell adhesion and/or an organized cytoskeleton. An in vitro kinase assay indicated that p105HEF1 was a substrate for Src. PP1, a specific Src kinase inhibitor, was able to block adhesion-dependent tyrosine phosphorylation of p105HEF1. These findings suggest that TGF-beta1 regulates HEF1 gene expression and that HEF1 phosphorylation is dependent on cell adhesion and Src kinase activity.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/Bicyclo Compounds, Heterocyclic,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochalasin D,
http://linkedlifedata.com/resource/pubmed/chemical/Dactinomycin,
http://linkedlifedata.com/resource/pubmed/chemical/NEDD9 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Synthesis Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Serine,
http://linkedlifedata.com/resource/pubmed/chemical/TGFB1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Thiazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Thiazolidines,
http://linkedlifedata.com/resource/pubmed/chemical/Threonine,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta1,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine,
http://linkedlifedata.com/resource/pubmed/chemical/latrunculin A
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
18
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pubmed:volume |
277
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
39599-608
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:12189134-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:12189134-Apoptosis,
pubmed-meshheading:12189134-Bicyclo Compounds, Heterocyclic,
pubmed-meshheading:12189134-Catalysis,
pubmed-meshheading:12189134-Cell Adhesion,
pubmed-meshheading:12189134-Cell Division,
pubmed-meshheading:12189134-Cell Line,
pubmed-meshheading:12189134-Cells, Cultured,
pubmed-meshheading:12189134-Cytochalasin D,
pubmed-meshheading:12189134-Cytoskeleton,
pubmed-meshheading:12189134-Dactinomycin,
pubmed-meshheading:12189134-Dose-Response Relationship, Drug,
pubmed-meshheading:12189134-Fibroblasts,
pubmed-meshheading:12189134-Gene Expression Regulation,
pubmed-meshheading:12189134-Humans,
pubmed-meshheading:12189134-Immunoblotting,
pubmed-meshheading:12189134-Phosphoproteins,
pubmed-meshheading:12189134-Phosphorylation,
pubmed-meshheading:12189134-Precipitin Tests,
pubmed-meshheading:12189134-Protein Binding,
pubmed-meshheading:12189134-Protein Synthesis Inhibitors,
pubmed-meshheading:12189134-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:12189134-Serine,
pubmed-meshheading:12189134-Signal Transduction,
pubmed-meshheading:12189134-Substrate Specificity,
pubmed-meshheading:12189134-Thiazoles,
pubmed-meshheading:12189134-Thiazolidines,
pubmed-meshheading:12189134-Threonine,
pubmed-meshheading:12189134-Time Factors,
pubmed-meshheading:12189134-Transcription, Genetic,
pubmed-meshheading:12189134-Transforming Growth Factor beta,
pubmed-meshheading:12189134-Transforming Growth Factor beta1,
pubmed-meshheading:12189134-Tyrosine,
pubmed-meshheading:12189134-Up-Regulation
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pubmed:year |
2002
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pubmed:articleTitle |
Regulation of HEF1 expression and phosphorylation by TGF-beta 1 and cell adhesion.
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pubmed:affiliation |
Center for Cell Biology & Cancer Research, Albany Medical College, Albany, New York 12208, USA. zhengm@mail.amc.edu
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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