IRAK: A Kinase Associated with the Interleukin-1 Receptor

TLDR

Interleukin‑1 signals through its type I receptor to activate NF‑κB, and the kinase IRAK, homologous to the Drosophila Pelle protein, is implicated in this pathway. The authors purified IRAK and cloned its complementary DNA to characterize the kinase. In cells overexpressing IL‑1RI or HeLa cells, IL‑1 exposure caused IRAK to rapidly associate with the IL‑1RI complex and become phosphorylated.

Abstract

The pleiotropic biological activities of interleukin-1 (IL-1) are mediated by its type I receptor (IL-1RI). When the ligand binds, IL-1RI initiates a signaling cascade that results in the activation of the transcription regulator nuclear factor kappa B (NF-kappa B). A protein kinase designated IRAK (IL-1 receptor-associated kinase) was purified, and its complementary DNA was molecularly cloned. When human embryonic kidney cells (cell line 293) over-expressing IL-1RI or HeLa cells were exposed to IL-1, IRAK rapidly associated with the IL-1RI complex and was phosphorylated. The primary amino acid sequence of IRAK shares similarity with that of Pelle, a protein kinase that is essential for the activation of a NF-kappa B homolog in Drosophila.