Phosphoinositide-mediated adaptor recruitment controls Toll-like receptor signaling.

@article{citeulike:1372894, abstract = {Toll-like receptors (TLRs) play a critical role in the immune system as sensors of microbial infection. Signaling downstream from TLRs is initiated by the recruitment of adaptor proteins, including MyD88 and TIRAP. These adaptors play essential roles in TLR signaling, but the mechanism of their function is currently unknown. Here we demonstrate that TIRAP and MyD88 have distinct functions and describe a mechanism of recruitment of TIRAP and MyD88 to TLR4. We find that TIRAP contains a phosphatidylinositol 4,5-bisphosphate (PIP2) binding domain, which mediates TIRAP recruitment to the plasma membrane. TIRAP then functions to facilitate MyD88 delivery to activated TLR4 to initiate signal transduction. These results establish that phosphoinositide-mediated adaptor recruitment initiates a specific signal-transduction pathway.}, address = {Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.}, author = {Kagan, J. C. and Medzhitov, R. }, citeulike-article-id = {1372894}, doi = {10.1016/j.cell.2006.03.047}, issn = {0092-8674}, journal = {Cell}, keywords = {tlr-signaling}, month = {June}, number = {5}, pages = {943--955}, posted-at = {2007-06-08 15:15:43}, priority = {2}, title = {Phosphoinositide-mediated adaptor recruitment controls Toll-like receptor signaling.}, url = {http://dx.doi.org/10.1016/j.cell.2006.03.047}, volume = {125}, year = {2006} }

TY - JOUR ID - citeulike:1372894 L3 - citeulike-article-id:1372894 TI - Phosphoinositide-mediated adaptor recruitment controls Toll-like receptor signaling. JF - Cell VL - 125 IS - 5 SP - 943 EP - 955 AD - Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA. SN - 0092-8674 N2 - Toll-like receptors (TLRs) play a critical role in the immune system as sensors of microbial infection. Signaling downstream from TLRs is initiated by the recruitment of adaptor proteins, including MyD88 and TIRAP. These adaptors play essential roles in TLR signaling, but the mechanism of their function is currently unknown. Here we demonstrate that TIRAP and MyD88 have distinct functions and describe a mechanism of recruitment of TIRAP and MyD88 to TLR4. We find that TIRAP contains a phosphatidylinositol 4,5-bisphosphate (PIP2) binding domain, which mediates TIRAP recruitment to the plasma membrane. TIRAP then functions to facilitate MyD88 delivery to activated TLR4 to initiate signal transduction. These results establish that phosphoinositide-mediated adaptor recruitment initiates a specific signal-transduction pathway. KW - tlr-signaling AU - Kagan, JC AU - Medzhitov, R PY - 2006/06/02/ UR - http://dx.doi.org/10.1016/j.cell.2006.03.047 ER -