Mutant Cells That Do Not Respond to Interleukin-1 (IL-1) Reveal a Novel Role for IL-1 Receptor-Associated Kinase

Mutant cells that do not respond to interleukin-1 (IL-1) reveal a novel role for IL-1 receptor-associated kinase.

Mutagenized human 293 cells containing an interleukin-1 (IL-1)-regulated herpes thymidine kinase gene, selected in IL-1 and gancyclovir, have yielded many independent clones that are unresponsive to IL-1. The four clones analyzed here carry recessive mutations and represent three complementation groups. Mutant A in complementation group I1 lacks IL-1 receptor-associated kinase (IRAK), while the...

Endotoxin IL - 1 Receptor - Associated Kinase Modulates

Cutting Edge: IL-1 receptor-associated kinase 4 structures reveal novel features and multiple conformations.

IL-1R-associated kinase (IRAK)4 plays a central role in innate and adaptive immunity, and is a crucial component in IL-1/TLR signaling. We have determined the crystal structures of the apo and ligand-bound forms of human IRAK4 kinase domain. These structures reveal several features that provide opportunities for the design of selective IRAK4 inhibitors. The N-terminal lobe of the IRAK4 kinase d...

Interleukin-1 (IL-1)-induced resistance to bacterial infection: role of the type I IL-1 receptor.

Pretreatment with a low dose of recombinant human interleukin-1 beta (IL-1) (3 to 30 micrograms/kg) 24 h before a lethal Pseudomonas aeruginosa infection prolongs survival in neutropenic mice. We investigated the role of the type I IL-1 receptor (IL-1RI) and IL-1RII in this IL-1-induced protection by using a specific IL-1 receptor antagonist (IL-1-Ra), which blocks effects mainly via IL-1RI. Pr...

Host Responsiveness to Endotoxin IL - 1 Receptor - Associated Kinase Modulates