Sorting out Toll signals.
Upon recognition of microbial products, Toll-like receptors (TLRs) recruit distinct combinations of adaptors to induce TLR-specific gene expression. In this issue, Kagan and Medzhitov (2006) demonstrate that the adaptor TIRAP/Mal localizes to the plasma membrane by binding to phosphatidylinositol 4,5-bisphosphate (PIP2). This binding recruits a key adaptor MyD88 to TLR4, suggesting that there is crosstalk between the TLR signaling pathway and phospholipid metabolism.
Fitzgerald
Katherine A
KA
Division of Infectious Disease and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA. kate.fitzgerald@umassmed.edu
Chen
Zhijian J
ZJ
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008563:Membrane Lipids / Q000378:metabolism*; D053594:Myeloid Differentiation Factor 88; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology; D017472:Receptors, Interleukin-1 / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; C507779:MYD88 protein, human; D008562:Membrane Glycoproteins; D008563:Membrane Lipids; D053594:Myeloid Differentiation Factor 88; D019269:Phosphatidylinositol 4,5-Diphosphate; D010743:Phospholipids; D017472:Receptors, Interleukin-1; C434984:TIRAP protein, human; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors