PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 9785472

Interleukin-1.

E Stylianou·J Saklatvala
View original source ↗Export metadata ↓

Abstract

Interleukin 1 (IL1) is a primary regulator of inflammatory and immune responses. Via its type I receptor it activates specific protein kinases, including the NF kappa B inducing kinase (NIK) and three distinct mitogen-activated protein (MAP) kinase cascades. These modulate a number of transcription factors including NF kappa B, AP1 and CREB each of which regulate a plethora of immediate early genes central to the inflammatory response. Phase I clinical trials of the soluble type I receptor and IRAP indicate that these have potential anti-inflammatory effects.

Explore related subjects

Adaptor Protein Complex 1Adaptor Protein Complex alpha SubunitsAdaptor Proteins, Vesicular TransportAnimalsCREB-Binding ProteinCalcium-Calmodulin-Dependent Protein KinasesEnzyme InductionGenes, Immediate-EarlyInflammationInterleukin 1 Receptor Antagonist ProteinInterleukin-1Membrane ProteinsNF-kappa BNuclear ProteinsReceptors, Interleukin-1Recombinant ProteinsSialoglycoproteinsTrans-ActivatorsJournal ArticleReview

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

E Stylianou, J Saklatvala. 1998. Interleukin-1.. https://doi.org/10.1016/s1357-2725(98)00081-8

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2000

Regulation of vascular endothelial growth factor expression in human keratinocytes by retinoids.

Vascular endothelial growth factor (VEGF) is overexpressed in hyperproliferative diseases, such as psoriasis and cancers, which are characterized by increased angiogenesis. Experimentally, VEGF overexpression can be induced by the treatment of cell cultures and biological tissues with phorbol esters, such as 12-O-tetradecanoylphorbol-13-acetate (TPA). Using normal human keratinocytes in conventional cultures and skin grafted onto nude mice in vivo, we show that retinoids can inhibit TPA-mediated VEGF gene induction at the transcriptional level. Because retinoids are biologically active either by interacting with the nuclear retinoic acid receptors or by interfering with the activator protein 1 (AP1) transcription factor, we studied the effect of the retinoic acid derivative CD 2409, which exhibits strong anti-AP1 activity but does not bind to the known retinoic acid receptors in vitro. The results demonstrate that the inhibition of VEGF expression by retinoids only depends on their anti-AP1 activity and does not require gene transactivation via retinoic acid response elements. Because the VEGF promoter contains four potential AP1 binding sites, we used different promoter constructs to identify the functional site responsible for TPA induction and retinoid inhibition. This site turned out to be localized at position -621 of the 5' flanking region of the VEGF gene.

Adaptor Protein Complex 1↗
PubMed1999

The leucine-based sorting motifs in the cytoplasmic domain of the invariant chain are recognized by the clathrin adaptors AP1 and AP2 and their medium chains.

Recognition of sorting signals within the cytoplasmic tail of membrane proteins by adaptor protein complexes is a crucial step in membrane protein sorting. The three known adaptor complexes, AP1, AP2, and AP3, have all been shown to recognize tyrosine- and leucine-based sorting signals, which are the most common sorting signals within membrane protein cytoplasmic tails. Although tyrosine-based signals are recognized by the micro-chains of adaptor complexes, the subunit recognizing leucine-based sorting signals is less clear. In this report we show by surface plasmon resonance that the two leucine-based sorting signals within the cytoplasmic tail of the invariant chain bind independently from each other to AP1 and AP2 but not to AP3. We also show that both motifs can be recognized by the micro-chains of AP1 and AP2. Moreover, by using monomeric as well as trimeric invariant chain constructs, we show that adaptor binding does not require trimerization of the invariant chain.

Adaptor Protein Complex 1↗