Interleukin-1-induced activation of the small GTPase Rac1 depends on receptor internalization and regulates gene expression.
Interleukin 1 (IL-1) triggers the internalization of its cognate receptor from the plasma membrane. We recently demonstrated that this internalization is of critical importance for the IL-1-induced gene expression. In this study we report that the IL-1-induced activation of the small GTPase Rac1 requires receptor endocytosis. We further show that the depletion of Rac1 reduces the IL-1-dependent gene expression without affecting signaling events that are initiated at the plasma membrane. Collectively, we provide evidence for a key role of Rac1 in a pathway that regulates IL-1-induced gene expression depending on receptor endocytosis.
Institute of Biochemistry, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany. Electronic address: Windheim.Mark@mh-hannover.de.
Mark
M
Windheim
Benjamin
B
Hansen
D034281:Dynamins / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D017930:Genes, Reporter; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
D007375:Interleukin-1; D016328:NF-kappa B; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D017472:Receptors, Interleukin-1; D020830:rac1 GTP-Binding Protein; D034281:Dynamins
Dynamin; Dynasore; Endocytosis; IL-1; MiTMAB; NF-κB; PAK1; PBD; Rac1; myristyl trimethyl ammonium bromide; p21-activated protein kinase 1; p21-binding domain