Bruton's tyrosine kinase (Btk)-the critical tyrosine kinase in LPS signalling?
The discovery of the Toll-like receptors (TLRs) has revolutionised the field of innate immunity. One unresolved question regarding LPS signalling is whether there is a role for tyrosine kinases downstream of the LPS receptor. Studies in mice deficient in Bruton's tyrosine kinase have previously shown that they are defective in their responses to LPS. Further investigation into the role of Btk in LPS signalling has directly implicated Btk downstream of TLR4, both with respect to p38 MAPK activation and activation of the transcription factor NFkappaB. In fact Btk is activated by LPS and has been shown to directly bind TLR4 and the key proximal signalling proteins involved in LPS-induced NFkappaB activation, MyD88, Mal and IRAK-1. These recent findings point to a direct role for Btk in LPS signal transduction and raise interesting questions regarding the mode of activation of Btk following LPS stimulation and the precise nature of the pathways activated downstream of Btk. A better understanding of how Btk functions in LPS signalling will have important implications for inflammatory and autoimmune disorders and therapies thereof.
Jefferies
Caroline A
CA
Department of Biochemistry and Biotechnology Institute, Cytokine Research Group, Trinity College, Dublin 2, Ireland. jefferca@tcd.ie
O'Neill
Luke A J
LA
D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D008070:Lipopolysaccharides / Q000276:immunology / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000276:immunology / Q000502:physiology*; D051379:Mice; D016328:NF-kappa B / Q000276:immunology / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000276:immunology / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000276:immunology / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology / Q000502:physiology*; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D011956:Receptors, Cell Surface; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625951:Btk protein, mouse