Linked Life Data

17727628

Source:http://linkedlifedata.com/resource/pubmed/id/17727628

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2007-10-26
pubmed:abstractText
Formyl peptide-receptor like-1 (FPRL-1) may possess critical roles in Alzheimer's diseases, chemotaxis and release of neurotoxins, possibly through its regulation of nuclear factor-kappaB (NFkappaB). Here we illustrate that activation of FPRL-1 in human U87 astrocytoma or Chinese hamster ovary cells stably expressing the receptor resulted in the phosphorylations of inhibitor-kappaB kinase (IKK), an onset kinase for NFkappaB signaling cascade. FPRL-1 selective hexapeptide Trp-Lys-Tyr-Met-Val-Met (WKYMVM) promoted IKK phosphorylations in time- and dose-dependent manners while pre-treatment of pertussis toxin abrogated the Galpha(i/o)-dependent stimulations. The FPRL-1-mediated IKK phosphorylation required extracellular signal-regulated protein kinase (ERK), phosphatidylinositol 3-kinase and cellular Src (c-Src), but not c-Jun N-terminal kinase and p38 mitogen-activated protein kinase. Despite its ability to mobilize Ca(2+), WKYMVM did not require Ca(2+) for the modulation of IKK phosphorylation. Activation of FPRL-1 also induced NFkappaB-driven luciferase expression. Interestingly, cholesterol depletion from plasma membrane by methyl-beta-cyclodextrin abolished the FPRL-1-stimulated IKK phosphorylation, denoting the important role of lipid raft integrity in the FPRL-1 to IKK signaling. Furthermore, we demonstrated that in U87 cells, several signaling intermediates in the FPRL-1-IKK pathway including Galpha(i2), c-Src and ERK were constitutively localized at the raft microdomains. WKYMVM administration not only resulted in higher amount of ERK recruitment to the raft region, but also specifically stimulated raft-associated c-Src and ERK phosphorylations. Taken together, these results demonstrate that FPRL-1 is capable of activating NFkappaB signaling through IKK phosphorylation and this may serve as a useful therapeutical target for FPRL-1-related diseases.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1471-4159
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
103
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1553-66
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Formyl peptide-receptor like-1 requires lipid raft and extracellular signal-regulated protein kinase to activate inhibitor-kappa B kinase in human U87 astrocytoma cells.
pubmed:affiliation
Department of Biochemistry, the Molecular Neuroscience Center, and the Biotechnology Research Institute, Hong Kong University of Science and Technology, Hong Kong, China.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't