Functional diversity and regulation of different interleukin-1 receptor-associated kinase (IRAK) family members.
Interleukin-1 receptor-associated kinase (IRAK) was first described as a signal transducer for the proinflammatory cytokine interleukin-1 (IL-1) and was later implicated in signal transduction of other members of the Toll-like receptor (TLR)/IL-1 receptor (IL-1R) family. In the meantime, four different IRAK-like molecules have been identified: two active kinases, IRAK-1 and IRAK-4, and two inactive kinases, IRAK-2 and IRAK-M. All IRAKs mediate activation of nuclear factor-kappaB (NF-kappaB) and mitogen-activated protein kinase (MAPK) pathways. Although earlier observations suggested that IRAKs have redundant functions, this hypothesis is now challenged by knockout studies. Furthermore, recent data imply a role for IRAK-1 in tumor necrosis factor receptor (TNFR) superfamily-induced signaling pathways as well. The scope of this review is to highlight the specific role of different IRAKs and to discuss several mechanisms that contribute to their activation and regulation.
Janssens
Sophie
S
Department of Molecular Biomedical Research, Unit of Molecular Signal Transduction in Inflammation, Ghent University, VIB, K.L. Ledeganckstraat 35, B-9000, Ghent, Belgium.
Beyaert
Rudi
R
D000595:Amino Acid Sequence; D000818:Animals; D029721:Drosophila Proteins; D015870:Gene Expression; D006801:Humans; D053592:Interleukin-1 Receptor-Associated Kinases; D008562:Membrane Glycoproteins / Q000502:physiology; D008954:Models, Biological; D008969:Molecular Sequence Data; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000502:physiology; D017472:Receptors, Interleukin-1 / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D051193:Toll-Like Receptors
D029721:Drosophila Proteins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D017472:Receptors, Interleukin-1; D051193:Toll-Like Receptors; D011494:Protein Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); C507771:IRAK3 protein, human; D053592:Interleukin-1 Receptor-Associated Kinases