High impact information on IRAK2

• Both hOGG1 and IRAK-2 were excluded as candidates for FANCD [1].
• Co-immunoprecipitation studies revealed that A52R interacted with both tumor necrosis factor receptor-associated factor 6 (TRAF6) and interleukin-1 receptor-associated kinase 2 (IRAK2) [2].
• In sharp contrast, we observe that the IRAK homolog, IRAK2, does not undergo degradation upon prolonged LPS treatment, suggesting complex regulation of the innate immunity network upon microbial challenge [3].
• The presence of the CTCF protein in human IRAK2 promoter was confirmed by chromatin immunoprecipitation assay [4].
• In all cell lines analyzed, including cells of lung, renal, monocytic and T-cell origin, the IRAK2 luciferase reporter construct, containing an intact CTCF-binding site, showed strong promoter activity [4].

Biological context of IRAK2

• An electrophoretic mobility shift assay of the DNA fragments containing the IRAK2 CpG island, revealed a single high-affinity binding site for the transcriptional regulator and a chromatin insulator protein, CTCF [4].
• Likewise, Akt association with IRAK2 is increased considerably by overexpression of PTEN (phosphatase and tensin homologue deleted on chromosome 10), while it is completely abrogated by overexpression of phosphoinositide-dependent protein kinase 1 [5].
• Interleukin-1-receptor-associated kinase 2 (IRAK2)-mediated interleukin-1-dependent nuclear factor kappaB transactivation in Saos2 cells requires the Akt/protein kinase B kinase [5].

Anatomical context of IRAK2

• Deletion of the ZIP or AP-2 sites did not significantly affect IRAK2 promoter activity in naive and endotoxin-treated mononuclear cells, in dormant and activated Jurkat T-cells, in lung and kidney cells [4].
• Antisense IRAK-2 ODN was delivered by lipofectin encapsulation into cultured endothelial cells [6].

Associations of IRAK2 with chemical compounds

• IRAK-2 plays a key role in the IL-1 signaling events leading to PGI2 release [7].
• Phosphorothioate oligodeoxynucleotide (ODN) was designed antisense to sequences of the recently cloned human IL-1 receptor associated kinase-2 (IRAK-2) [6].

Physical interactions of IRAK2

• This assay revealed a CTCF-binding site within the mouse Irak2 promoter [4].

Regulatory relationships of IRAK2

• Transcriptional regulator CTCF controls human interleukin 1 receptor-associated kinase 2 promoter [4].
• IL-1-induced ICAM-1 mRNA expression was also inhibited after treatment of cells with antisense IRAK-2 ODN 3 microg for 8 h [6].
• Antisense IRAK-2 oligonucleotide blocks IL-1-stimulated NF-kappaB activation and ICAM-1 expression in cultured endothelial cells [6].
• AIM: To study the inhibitory effects of antisense interleukin-1 receptor associated kinase-2 (IRAK-2) oligodeoxynucleotide (ODN) on interleukin-1 (IL-1)-stimulated nuclear factor-kappa B (NF-kappa B) activation [8].
• Knockdown of IRAK-2 expression by small interfering RNA suppressed TLR3, TLR4, and TLR8 signaling to NFkappaB in human cell lines, and importantly, TLR4-mediated chemokine production in primary human cells [9].

Other interactions of IRAK2

• In this paper, we report that IRAK2 and MyD88, but not IRAK1, interact physically with Akt, as demonstrated by co-immunoprecipitation and pull-down experiments [5].
• Interestingly, the association of Akt with recombinant IRAK2 is decreased by stimulation with IL-1, and is favoured by pre-treatment with phosphatase [5].
• METHODS: The HUVEC were transfected with antisense IRAK-2 ODN and stimulated with IL-1 and TNF [7].
• A maximum inhibition of NF-KB activation or surface expression of ICAM-1 occurred when the cells were incubated with antisense IRAK-2 ODN 3 microg for 8 h [6].
• The attenuation of the cellular response to IL-1 caused by antisense IRAK-2 ODN correlated with a reduction of IRAK-2 expression [6].

Analytical, diagnostic and therapeutic context of IRAK2

• The levels of NF-KB, surface expression of intracellular adhesion molecule-1 (ICAM-1), ICAM-1 and IRAK-2 mRNAs were measured by sandwich ELISA, ELISA on cells in situ, and semiquantitative reverse transcription-PCR (RT-PCR), respectively [6].

References