※ IRAK family introduction

    IRAK (Interleukin-1 receptor-associated kinase) belong to TKL family. Four genes encoding IRAKs have been identified in human genome, IRAK1, IRAK2, IRAK3 (IRAKM) and IRAK4. All IRAKs are involved in activating transcript factor NF-kB. IRAK1 has two signature forms with one unmodified 85kD form localized mainly in cytoplasm and 100kD form in nucleus. This suggests that the modification may be essential for IRAK1 trafficking from cytoplasm into nucleus and performs the function. Studies show that IRAK1 can mediate the activation of STAT3 which is important for the expression of IL-10 gene; moreover evidence also indicates that IRAK1 can directly bind to the promoter of IL-10 gene and regulate the expression. IRAK2 gene encodes a 590-amino acid protein with the size of 65kD. Overexpression of IRAK2 can be associated with MyD88 and TRAF6 and mediate the activation of NF-kB. IRAK2 is also involved in regualtion of cellular apoptosis. IRAKM gene encodes a 596-amino acid and 68kD protein. IRAKM expression has been identified in the peripheral blood leukocytes and monocytic cell lines. Overexpression of IRAKM also actives NF-kB. IRAK4 gene encodes a 460-amino acid and 52kD protein kinase. IRAK4 knockout mice display the defects of NF-kB activation and various inflammatory cytokines expression. Evidence also shows that IRAK4 is the primary kinase in the TLR signaling pathway and key regulator for the NF-kB activation. IRAK4 defect always associated with human disease, including persistent pyogenic bacteria infection and poor inflammatory responses (1).

Reference
1. Huang, Y.S., Misior, A. and Li, L.W. (2005) Novel role and regulation of the interleukin-1 receptor associated kinase (IRAK) family proteins. Cell Mol Immunol, 2, 36-39. PMID: 16212909