Linked Life Data

17878165

Source:http://linkedlifedata.com/resource/pubmed/id/17878165

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
48
pubmed:dateCreated
2007-11-26
pubmed:abstractText
Members of the guanine exchange factor (GEF) family of scaffold proteins are involved in the integration of signal flow downstream of many receptors in adaptive immunity. However, the full complement of GEFs that function downstream of Toll-like receptors (TLRs) requires further identification and functional understanding. By systematically integrating expression profiles from immune and epithelial cells with functional studies, we demonstrate that protein kinase A anchoring protein 13 (AKAP13), a scaffold protein with GEF activity, is an activator of NF-kappaB downstream of TLR2 signaling. Stimulation of the human macrophage cell line THP-1 and epithelial cells with a TLR2 ligand caused a significant up-regulation in AKAP13 mRNA, corresponding to an increase in protein expression. Analysis of TLR2 reporter cell lines deficient in AKAP13 expression revealed significantly reduced NF-kappaB activation and reduced secretion of interleukin-8 and MCP-1 in response to specific ligand stimulation. Furthermore, NF-kappaB activation was partially inhibited by a GEF-deficient AKAP13 mutant. AKAP13 was also involved in phosphorylation of JNK but not of extracellular signal-regulated kinase ERK1 and -2 following ligand stimulation. Together, our results suggest that AKAP13 plays a role in TLR2-mediated NF-kappaB activation and suggest that GEF-containing scaffold proteins may confer specificity to innate immune responses downstream of TLRs.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/A Kinase Anchor Proteins, http://linkedlifedata.com/resource/pubmed/chemical/AKAP13 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Guanine Nucleotide Exchange Factors, http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3, http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins, http://linkedlifedata.com/resource/pubmed/chemical/TLR2 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Tlr2 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptor 2, http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein..., http://linkedlifedata.com/resource/pubmed/chemical/rhoA GTP-Binding Protein
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
30
pubmed:volume
282
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
35308-17
pubmed:dateRevised
2011-10-31
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
AKAP13, a RhoA GTPase-specific guanine exchange factor, is a novel regulator of TLR2 signaling.
pubmed:affiliation
Gastroenterology Unit, Center for Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural