LPS Stimulated MAPK Signaling
Lipopolysaccharides (LPS) are major cell wall constituents of Gram-negative bacteria that bind to LPS-binding proteins (LBP) in plasma. The LPS-LBP complex interacts with CD14 to form a ternary complex, LPS:LBP:CD14, which transfers LPS to the toll-like receptor 4 (TLR4) accessory protein MD2 complex. This leads to activation of toll-like receptor-4. LPS activated TRL4 activates the NFkappaB pathway and all three MAPK pathways; ERK, JNK/SAPK and p38. Activation of the NFkappB pathway is complex. It requires activation of phosphatidylinositol-3-kinase (PI3K) upstream of IkappaBalpha degradation. A second NFkappaB activation pathway follows the sequence: TLR4, MyD88, TIR, IRAK1, TRAF6, NIK, IKK, IkappaB, NFkappaB.
ERK is activated by LPS activated TLFR4 through Raf1. LPS activated TLFR4 activates the Raf1/MEK/ERK pathway both by p21Ras-GTPase-dependent and Ras-independent mechanisms. Lipopolysaccharides (LPS) are major cell wall constituents of Gram-negative bacteria that bind to LPS-binding proteins (LBP) in plasma. The LPS-LBP complex interacts with CD14 to form a ternary complex, LPS:LBP:CD14, which transfers LPS to the toll-like receptor 4 (TLR4) accessory protein MD2 complex. This leads to activation of toll-like receptor-4. LPS activated TRL4 activates the NFkappaB pathway and all three MAPK pathways; ERK, JNK/SAPK and p38. Activation of the NFkappB pathway is complex. It requires activation of phosphatidylinositol-3-kinase (PI3K) upstream of IkappaBalpha degradation. A second NFkappaB activation pathway follows the sequence: TLR4, MyD88, TIR, IRAK1, TRAF6, NIK, IKK, IkappaB, NFkappaB. ERK is activated by LPS activated TLFR4 through Raf1. LPS activated TLFR4 activates the Raf1/MEK/ERK pathway both by p21Ras-GTPase-dependent and Ras-independent mechanisms.
|
