Interleukin-1-induced intracellular signaling pathways converge in the activation of mitogen-activated protein kinase and mitogen-activated protein kinase-activated protein kinase 2 and the subsequent phosphorylation of the 27-kilodalton heat shock protein in monocytic cells.
Interleukin (IL)-1 plays a central role in human host defense. Binding of IL-1 to its receptor is associated with phosphorylation of various cellular target proteins, most of which are unidentified. The kinases responsible for target protein phosphorylation after IL-1 stimulation are also still not completely understood. We report here that IL-1 induced activation of mitogen-activated protein (MAP) kinase in primary monocytes and in the human monocytic leukemia cell line U-937. Activation of MAP kinase was followed by activation of MAP kinase-activated protein (MAPKAP) kinase 2, a serine/threonine kinase, leading to subsequent phosphorylation of the small heat shock protein [27-kDa heat shock protein (Hsp27)]. Phosphorylation of Hsp27 triggered by IL-1 was both dose and time dependent. IL-1 failed to phosphorylate Hsp27 when cells had been previously deactivated with tyrosine kinase inhibitors such as genistein. In those cells, however, Hsp27 phosphorylation could be reconstituted when activated immunoprecipitated MAP kinase or purified MAPKAP kinase 2 was added. Phosphorylation of Hsp27 could also be inhibited when NaF, a serine/threonine phosphatase inhibitor, was omitted. Taken together, our findings indicate that IL-1-induced intracellular signaling pathways converge in the activation of MAP kinase and MAPKAP kinase 2 and the subsequent phosphorylation of Hsp27.
Ahlers
A
A
Max Delbrück Center for Molecular Medicine, Berlin, Germany.
Belka
C
C
Gaestel
M
M
Lamping
N
N
Sott
C
C
Herrmann
F
F
Brach
M A
MA
D002460:Cell Line; D004790:Enzyme Induction / Q000187:drug effects; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins; D009000:Monocytes / Q000201:enzymology / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013379:Substrate Specificity; D000099190:MAP-Kinase-Activated Kinase 2
D006360:Heat-Shock Proteins; D007375:Interleukin-1; D047908:Intracellular Signaling Peptides and Proteins; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D000099190:MAP-Kinase-Activated Kinase 2