Linked Life Data

10340949

Source:http://linkedlifedata.com/resource/pubmed/id/10340949

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1999-7-7
pubmed:abstractText
We hypothesized that in bovine tracheal myocytes, growth factor treatment induces transcription from the cyclin D1 promoter that is dependent on the activation of both Ras and extracellular signal-related kinase (ERK). We found that platelet-derived growth factor (PDGF) treatment induced substantial activation of ERK2 that was blocked by expression of a dominant-negative Ha-Ras. Further, expression of a constitutively active Ha-Ras induced substantial ERK2 activity, consistent with the notion that Ras is required and sufficient for ERK activation. PDGF treatment induced only modest activation of the Jun amino terminal kinase-1 (JNK1) and p38 mitogen-activated protein kinases (MAPKs). Active Ras induced similar responses, implying that complete activation of the JNK and p38 pathways requires additional or alternative upstream signaling intermediates besides Ras. In contrast, expression of a constitutively active Rac1, an alternative guanosine triphosphatase involved in intracellular signaling, produced a high level of JNK1 activation, suggesting that Rac1 is an important upstream activator of JNK in this system. Active Ras and MAPK/ ERK kinase-1 (MEK1) (the upstream activator of ERK) each induced cyclin D1 promoter activity, whereas active stress-activated protein kinase/ERK kinase-1 (SEK1), an upstream activator of JNK, did not. Finally, the synthetic MEK inhibitor PD98059 blocked Ras-induced cyclin D1 promoter activity. Together, these data suggest that in bovine tracheal myocytes: (1) activation of MAPK by PDGF is dependent on Ras; (2) active Ras is sufficient for ERK activation but is insufficient for maximal activation of JNK or p38; (3) activation of Rac1 is sufficient for maximal JNK activation; and (4) Ras, MEK, and ERK constitute a distinct pathway to cyclin D1 transcriptional activation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1044-1549
pubmed:author
pubmed:issnType
Print
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1294-302
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:10340949-Animals, pubmed-meshheading:10340949-Calcium-Calmodulin-Dependent Protein Kinases, pubmed-meshheading:10340949-Cattle, pubmed-meshheading:10340949-Cells, Cultured, pubmed-meshheading:10340949-GTP-Binding Proteins, pubmed-meshheading:10340949-Genes, bcl-1, pubmed-meshheading:10340949-Genes, ras, pubmed-meshheading:10340949-Humans, pubmed-meshheading:10340949-JNK Mitogen-Activated Protein Kinases, pubmed-meshheading:10340949-Mitogen-Activated Protein Kinase 1, pubmed-meshheading:10340949-Mitogen-Activated Protein Kinases, pubmed-meshheading:10340949-Muscle, Smooth, pubmed-meshheading:10340949-Platelet-Derived Growth Factor, pubmed-meshheading:10340949-Proto-Oncogene Proteins c-jun, pubmed-meshheading:10340949-Signal Transduction, pubmed-meshheading:10340949-Trachea, pubmed-meshheading:10340949-Transcription, Genetic, pubmed-meshheading:10340949-p38 Mitogen-Activated Protein Kinases, pubmed-meshheading:10340949-rac GTP-Binding Proteins
pubmed:year
1999
pubmed:articleTitle
Platelet-derived growth factor stimulation of mitogen-activated protein kinases and cyclin D1 promoter activity in cultured airway smooth-muscle cells. Role of Ras.
pubmed:affiliation
Department of Pediatrics, University of Chicago, Chicago, Illinois 60637-1470, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't