Cellular trafficking of the IL-1RI-associated kinase-1 requires intact kinase activity.
Upon stimulation of cells with interleukin-1 (IL-1) the IL-1 receptor type I (IL-1RI) associated kinase-1 (IRAK-1) transiently associates to and dissociates from the IL-1RI and thereafter translocates into the nucleus. Here we show that nuclear translocation of IRAK-1 depends on its kinase activity since translocation was not observed in EL-4 cells overexpressing a kinase negative IRAK-1 mutant (EL-4(IRAK-1-K239S)). IRAK-1 itself, an endogenous substrate with an apparent molecular weight of 24kDa (p24), and exogenous substrates like histone and myelin basic protein are phosphorylated by nuclear located IRAK-1. Phosphorylation of p24 cannot be detected in EL-4(IRAK-1-K239S) cells. IL-1-dependent recruitment of IRAK-1 to the IL-1RI and subsequent phosphorylation of IRAK-1 is a prerequisite for nuclear translocation of IRAK-1. It is therefore concluded that intracellular localization of IRAK-1 depends on its kinase activity and that IRAK-1 may also function as a kinase in the nucleus as shown by a new putative endogenous substrate.
Böl
Gaby-Fleur
GF
German Institute of Human Nutrition Potsdam-Rehbruecke, Biochemistry of Micronutrients, 14558 Nuthetal, Germany. boel@mail.dife.de
Jurrmann
Nadine
N
Brigelius-Flohé
Regina
R
D021581:Active Transport, Cell Nucleus; D000818:Animals; D002460:Cell Line; D004789:Enzyme Activation; D007375:Interleukin-1 / Q000378:metabolism*; D053592:Interleukin-1 Receptor-Associated Kinases; D051379:Mice; D011494:Protein Kinases / Q000378:metabolism*; D017472:Receptors, Interleukin-1 / Q000378:metabolism*; D053573:Receptors, Interleukin-1 Type I; D015398:Signal Transduction; D013945:Thymoma / Q000378:metabolism*
D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D053573:Receptors, Interleukin-1 Type I; D011494:Protein Kinases; D053592:Interleukin-1 Receptor-Associated Kinases