Activation of c-Jun N-terminal kinase by human granulocyte macrophage-colony stimulating factor in BA/F3 cells.
Human granulocyte-macrophage colony-stimulating factor (hGM-CSF) induces various signaling events in hematopoietic cells. We reported that there are at least two distinct pathways of hGM-CSF signals, one for activation of proliferation and the other one for activation of c-fos promoter through the MAPK cascade. Activation of other members of the MAPK family, c-Jun N-terminal kinase (JNK) and p38 MAPK under various cellular stress have also been reported. We found that hGM-CSF activates JNK in BA/F3 cells expressing the hGM-CSF receptor (hGMR) and that activation depends on a membrane proximal region including box1 and requires a more membrane distal region of hGMR beta subunit (beta c). There are 8 known tyrosine (tyr) residues in the cytoplasmic region of beta c. Mutant beta c lacking all the tyr residues hardly activates JNK, thereby indicating that the tyr residue(s) is essential for the activation of JNK. Mutation analyses of each tyr residue indicated that none of the tyr residues seems essential for the activation of JNK, indicating multiple tyr residues play a similar function to transduce signals for this activation.
Liu
R
R
Department of Molecular and Developmental Biology, Institute of Medical Science, University of Tokyo, Minato-ku, Japan.
Itoh
T
T
Arai
K
K
Watanabe
S
S
D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002460:Cell Line; D004789:Enzyme Activation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics; D015398:Signal Transduction
D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases