Mitogen-activated protein kinases and ribosomal S6 protein kinases are involved in signaling pathways shared by interleukin-11, interleukin-6, leukemia inhibitory factor, and oncostatin M in mouse 3T3-L1 cells.
The mechanisms of signaling pathways shared by interleukin (IL)-11, IL-6, leukemia inhibitory factor (LIF), and oncostatin M (ONC) remain elusive. We report here that treatment of 3T3-L1 cells with IL-11, IL-6, LIF, and ONC induces overlapping but distinct patterns of tyrosine phosphorylation and activates indistinguishable primary response genes. We further demonstrate for the first time that IL-11, IL-6, LIF, and ONC can trigger the activation of mitogen-activated protein kinases and the 85-92-kDa ribosomal S6 protein kinase (pp90rsk). In addition, our data also show that preincubation of cells with a tyrosine kinase inhibitor herbimycin A, but not with a serine/threonine kinase inhibitor H7, blocks activation of mitogen-activated protein kinases and pp90rsk. Interestingly, H7, but not herbimycin A, inhibits pp90rsk activity in the in vitro kinase assays. These results suggest that pp90rsk is one of the potential candidates for the H7-sensitive protein kinase(s), which is critical for the activation of primary response genes by these cytokines.
Yin
T
T
Department of Medicine (Hematology/Oncology), Indiana University School of Medicine, Indianapolis 46202.
Yang
Y C
YC
D016475:3T3 Cells; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D017370:Interleukin-11 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D007700:Kinetics; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000494:pharmacology*; D051379:Mice; D053683:Oncostatin M; D010455:Peptides / Q000494:pharmacology*; D010750:Phosphoproteins / Q000302:isolation & purification / Q000378:metabolism; D019000:Phosphotyrosine; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D019893:Ribosomal Protein S6 Kinases; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014158:Transcription, Genetic; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D006131:Growth Inhibitors; D017370:Interleukin-11; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008222:Lymphokines; C508351:OSM protein, human; C508352:Osm protein, mouse; D010455:Peptides; D010750:Phosphoproteins; D011994:Recombinant Proteins; D053683:Oncostatin M; D019000:Phosphotyrosine; D014443:Tyrosine; D017346:Protein Serine-Threonine Kinases; D019893:Ribosomal Protein S6 Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases