TIRAP binds PIP2-rich regions in the plasma membrane

Stable Identifier
Homo sapiens
MAL binds PIP2-rich regions in the plasma membrane
Locations in the PathwayBrowser
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

Upon LPS stimulation, Mal(TIRAP) was shown to bind to PIP2-rich regions on the cell surface trough its phosphatidylinositol 4,5-bisphosphate-binding domain [Kagan JC and Medzithov R 2007]. TLR2 or 4 associates with Mal(TIRAP) on the cell surface, which in turn facilitates the binding of MyD88 to the activated TLR, leading to NF-kB and MAPK activation [Nunez Miguel R et al 2007, Nagpal K et al 2009].

Literature References
PubMed ID Title Journal Year
11544529 Mal (MyD88-adapter-like) is required for Toll-like receptor-4 signal transduction

Jefferies, CA, O'Neill, LA, Mansell, AS, Bird, TA, Brint, E, Smith, DE, Gray, P, Sims, JE, Palsson-McDermott, EM, Bowie, AG, Harte, MT, Fitzgerald, KA, McMurray, D, Dunne, A, Brady, G

Nature 2001
16751103 Phosphoinositide-mediated adaptor recruitment controls Toll-like receptor signaling

Kagan, JC, Medzhitov, R

Cell 2006
19509286 A TIR domain variant of MyD88 adapter-like (Mal)/TIRAP results in loss of MyD88 binding and reduced TLR2/TLR4 signaling

Plantinga, TS, Fitzgerald, KA, Netea, MG, Nagpal, K, Monks, BG, Wong, J, Gay, NJ, Golenbock, DT

J. Biol. Chem. 2009
15585605 TIRAP/Mal, TRIF and TRAM. Differential utilization of these TIR

Takeda, K, Akira, S

Int Immunol 2005
Orthologous Events
Cite Us!