Linked Life Data

11060298

Source:http://linkedlifedata.com/resource/pubmed/id/11060298

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2001-5-23
pubmed:abstractText
Several signaling pathways are activated by all-trans-retinoic acid (RA) to mediate induction of differentiation and apoptosis of malignant cells. In the present study we provide evidence that the p38 MAP kinase pathway is activated in a RA-dependent manner in the NB-4, acute pro-myelocytic leukemia, and the MCF-7, breast carcinoma, cell lines. RA treatment of cells induces a time- and dose-dependent phosphorylation of p38, and such phosphorylation results in activation of its catalytic domain. p38 activation is not inducible by RA in a variant NB-4 cell line, NB-4.007/6, which is resistant to the effects of RA, suggesting a role for this pathway in the induction of RA responses. Our data also demonstrate that the small G-protein Rac1 is activated by RA and functions as an upstream regulator of p38 activation, whereas the MAPKAPK-2 serine kinase is a downstream effector for the RA-activated p38. To obtain information on the functional role of the Rac1/p38/MAPKAPK-2 pathway in RA signaling, the effects of pharmacological inhibition of p38 on RA-induced gene transcription and cell differentiation were determined. Our results indicate that treatment of cells with the SB203580 inhibitor does not inhibit RA-dependent gene transcription via retinoic acid response elements or induction of Stat1 protein expression. However, treatment with SB203580 or SB202190 strongly enhances RA-dependent induction of cell differentiation and RA-regulated growth inhibitory responses. Altogether, our findings demonstrate that the Rac1/p38 MAP kinase pathway is activated in a RA-dependent manner and exhibits negative regulatory effects on the induction of differentiation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/4-(4-fluorophenyl)-2-(4-hydroxypheny..., http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Imidazoles, http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides..., http://linkedlifedata.com/resource/pubmed/chemical/MAP-kinase-activated kinase 2, http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Pyridines, http://linkedlifedata.com/resource/pubmed/chemical/SB 203580, http://linkedlifedata.com/resource/pubmed/chemical/Tretinoin, http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein..., http://linkedlifedata.com/resource/pubmed/chemical/rac1 GTP-Binding Protein
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
9
pubmed:volume
276
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4012-9
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Activation of Rac1 and the p38 mitogen-activated protein kinase pathway in response to all-trans-retinoic acid.
pubmed:affiliation
Section of Hematology-Oncology, Department of Medicine, University of Illinois and West Side Veterans Affairs Medical Center, Chicago, Illinois 60607, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.