Oncostatin M induces association of Grb2 with Janus kinase JAK2 in multiple myeloma cells.
Oncostatin M (OSM) is a 28-kD glycoprotein recently identified as a growth factor for human multiple myeloma cells. It belongs to a family of distantly related cytokines that includes interleukin 6, ciliary neurotrophic factor, leukemia-inhibitory factor, and interleukin 11. These cytokines initiate signaling by inducing either homodimerization of gp130 or heterodimerization of gp130 with leukemia-inhibitory factor receptor beta components. Such dimerization in turn activates receptor-associated tyrosine kinases. In the present study using U266B1 human multiple myeloma cells, we show that OSM induces tyrosine phosphorylation and activation of JAK2, but not JAK1 or Tyk2, kinases. The results also demonstrate that OSM induces direct interaction of JAK2 kinase with Grb2, an SH2/SH3 domain containing adaptor protein. The SH2 domain of Grb2 is directly associated with tyrosine-phosphorylated JAK2. Furthermore, the presence of Sos in the JAK2-Grb2 complex suggests a role for Ras in OSM-transduced signaling.
D048868:Adaptor Proteins, Signal Transducing; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D066246:ErbB Receptors / Q000378:metabolism*; D051380:GRB2 Adaptor Protein; D006801:Humans; D053614:Janus Kinase 2; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000378:metabolism; D053683:Oncostatin M; D010455:Peptides / Q000494:pharmacology*; D019000:Phosphotyrosine / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D015398:Signal Transduction; D020664:Son of Sevenless Proteins; D018909:src Homology Domains
D048868:Adaptor Proteins, Signal Transducing; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; D046911:Macromolecular Substances; D008565:Membrane Proteins; C508351:OSM protein, human; D010455:Peptides; D011506:Proteins; D011518:Proto-Oncogene Proteins; D020664:Son of Sevenless Proteins; D053683:Oncostatin M; D019000:Phosphotyrosine; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; D053614:Janus Kinase 2