Source:http://linkedlifedata.com/resource/pubmed/id/16027723
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
53
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pubmed:dateCreated |
2005-11-24
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pubmed:abstractText |
Proliferation of nontransformed cells is regulated by cell-cell contacts, which are referred to as contact-inhibition. Despite its generally accepted importance for cell cycle control, knowledge about the intracellular signalling pathways involved in contact inhibition is scarce. In the present work we show that p38alpha mitogen-activated protein kinase (MAPK) is involved in the growth-inhibitory signalling cascade of contact inhibition in fibroblasts. p38alpha activity is increased in confluent cultures of human fibroblasts compared to proliferating cultures. Time course studies show a sustained activation of p38alpha in response to cell-cell contacts in contrast to a transient activation after serum stimulation. The induction of contact inhibition by addition of glutaraldehyde-fixed cells is impaired by pharmacological inhibition of p38 as well as in p38alpha-/- fibroblasts. Further evidence for a central role of p38alpha in contact inhibition comes from the observation that p38alpha-/- fibroblasts show a higher saturation density compared to wild-type (wt) fibroblasts, which is reversed by reconstituted expression of p38alpha. In agreement with a defect in contact inhibition, p27(Kip1) accumulation is impaired in p38alpha-/- fibroblasts compared to wt fibroblasts. Hence, our work shows a new role for p38alpha in contact inhibition and provides a mechanistic basis for the recently proposed tumour suppressive function of this MAPK pathway.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0950-9232
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
24
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pubmed:volume |
24
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
7941-5
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:16027723-Cell Culture Techniques,
pubmed-meshheading:16027723-Cell Proliferation,
pubmed-meshheading:16027723-Cell Transformation, Neoplastic,
pubmed-meshheading:16027723-Contact Inhibition,
pubmed-meshheading:16027723-Fibroblasts,
pubmed-meshheading:16027723-Humans,
pubmed-meshheading:16027723-Mitogen-Activated Protein Kinase 14,
pubmed-meshheading:16027723-Neoplasms,
pubmed-meshheading:16027723-Signal Transduction
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pubmed:year |
2005
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pubmed:articleTitle |
p38alpha MAPK is required for contact inhibition.
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pubmed:affiliation |
Institute of Toxicology, Johannes Gutenberg-University, Obere Zahlbacherstr. 67, 55131 Mainz, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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