+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Differential regulation and role of interleukin-1 receptor associated kinase-M in innate immunity signaling



Differential regulation and role of interleukin-1 receptor associated kinase-M in innate immunity signaling



Cellular Signalling 19(7): 1596-1601



Toll-like-receptor mediated signaling is finely regulated by a complex intracellular protein network including the interleukin-1 receptor associate kinases (IRAKs). IRAK-4, 1, and 2 may positively regulate innate immunity signaling through the activation of various downstream kinases such as MAPKs. In contrast, IRAK-M plays an inhibitory role through unknown mechanism. In this report, we show that IRAK-M is ubiquitously present in the cell, and becomes exclusively cytoplasmic upon bacterial lipoprotein Pam(3)CSK(4) challenge. Furthermore, using bone marrow derived macrophages (BMDM) from wild type, IRAK1(-/-), and IRAK-M(-/-) mice, we have herein demonstrated that IRAK-M selectively attenuates bacterial lipopeptide Pam(3)CSK(4)-induced p38 activation, but not ERK or JNK. IRAK1(-/-) and IRAK-M(-/-)BMDM display distinct activation profile of various MAP kinases upon Pam(3)CSK(4) challenge, indicating that IRAK-M exerts its inhibitory effect through an IRAK1 independent pathway. Pam(3)CSK(4) challenge leads to rapid decrease of MKP-1 protein level in IRAK-M(-/-)BMDM as well as THP-1 cells with decreased IRAK-M expression through siRNA interference. Our findings indicate that IRAK-M selectively attenuates p38 activation and inhibits innate immunity through stabilizing MKP-1.

(PDF emailed within 0-6 h: $19.90)

Accession: 015510436

Download citation: RISBibTeXText

PMID: 17379480

DOI: 10.1016/j.cellsig.2007.02.009


Related references

Differential effects of interleukin-17 receptor signaling on innate and adaptive immunity during central nervous system bacterial infection. Journal of Neuroinflammation 9: 128, 2013

Differential effects of interleukin-17 receptor IL-17R signaling on innate and adaptive immunity during central nervous system bacterial infection. 2012

A mammalian like interleukin-1 receptor-associated kinase 4 (IRAK-4), a TIR signaling mediator in intestinal innate immunity of black tiger shrimp (Penaeus monodon). Biochemical and Biophysical Research Communications 417(1): 623-629, 2012

Tyrosine-610 in the Receptor Kinase BAK1 Does Not Play a Major Role in Brassinosteroid Signaling or Innate Immunity. Frontiers in Plant Science 8: 1273, 2017

Phosphorylation-dependent differential regulation of plant growth, cell death, and innate immunity by the regulatory receptor-like kinase BAK1. Plos Genetics 7(4): E1002046, 2011

Toll-like receptor cross-hyporesponsiveness is functional in interleukin-1-receptor-associated kinase-1 (IRAK-1)-deficient macrophages: differential role played by IRAK-1 in regulation of tumour necrosis factor and interleukin-10 production. Scandinavian Journal of Immunology 67(5): 473-479, 2008

Differential regulation of key signaling molecules in innate immunity and human diseases. Advances in Experimental Medicine and Biology 598: 49-61, 2007

Interleukin-1 receptor-associated kinase 4 links innate immunity to the pathogenesis of rheumatoid arthritis. Arthritis and Rheumatism 60(6): 1571-1574, 2009

Regulation of Toll-like receptor signaling in the innate immunity. Science China. Life Sciences 53(1): 34-43, 2010

Identification of optineurin as an interleukin-1 receptor-associated kinase 1-binding protein and its role in regulation of MyD88-dependent signaling. Journal of Biological Chemistry 292(42): 17250-17257, 2017

BSK1, a receptor-like cytoplasmic kinase, involved in both BR signaling and innate immunity in Arabidopsis. Plant Signaling and Behavior 8(8), 2014

LYK4, a lysin motif receptor-like kinase, is important for chitin signaling and plant innate immunity in Arabidopsis. Plant Physiology 160(1): 396-406, 2013

Lyk4, a Lysin Motif Receptor-Like Kinase, Is Important for Chitin Signaling and Plant Innate Immunity in Arabidopsis. Plant Physiology 160(1): 396-406, 2012

Role of the JAK/STAT signaling pathway in regulation of innate immunity in neuroinflammatory diseases. Clinical Immunology 189: 4-13, 2016

Differential regulation of the interleukin-12 receptor during the innate immune response to Leishmania major. Infection and Immunity 66(8): 3818-3824, 1998