Oncostatin M and leukemia inhibitory factor trigger overlapping and different signals through partially shared receptor complexes.
Leukemia inhibitory factor (LIF) and oncostatin M (OSM) both bind to the same receptor with high affinity and thus mediate an overlapping spectrum of biological activities, the signal transduction mechanisms for which are unclear. We show that mitogen-activated protein kinases are involved in both the LIF and OSM signal transduction pathways. However, we found that OSM is a much more potent inducer of both mitogen-activated protein kinase activity and biological response, both of which correlate with the expression of a second OSM receptor that does not bind LIF. In addition, different patterns of tyrosine-phosphorylated proteins were stimulated by OSM and LIF. We therefore suggest that the two receptors for OSM can be coupled to different signal transduction events.
Thoma
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Department of Biochemistry, Immunex Corporation, Seattle, Washington 98101.
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D000595:Amino Acid Sequence; D002460:Cell Line; D004789:Enzyme Activation; D006131:Growth Inhibitors / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008222:Lymphokines / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1; D008969:Molecular Sequence Data; D053683:Oncostatin M; D010455:Peptides / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D018121:Receptors, Cytokine / Q000378:metabolism*; D053606:Receptors, OSM-LIF; D053677:Receptors, Oncostatin M; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism
D006131:Growth Inhibitors; D015850:Interleukin-6; C507837:LIF protein, human; C507840:LIFR protein, human; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008222:Lymphokines; C508351:OSM protein, human; D010455:Peptides; D018121:Receptors, Cytokine; D053606:Receptors, OSM-LIF; D053677:Receptors, Oncostatin M; D053683:Oncostatin M; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D019950:Mitogen-Activated Protein Kinase 1