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) induc es various signaling events in hematopoietic cells. We reported that t here are at least two distinct pathways of hGM-CSF signals, one for ac tivation of proliferation and the other one for activation of c-fos pr omoter through the MAPK cascade. Activation of other members of the MA PK family, c-Jun N-terminal kinase (JNK) and p38 MAPK under various ce llular stress have also been reported. We found that hGM-CSF activates JNK in BA/F3 cells expressing the hGM-CSF receptor (hGMR) and that ac tivation depends on a membrane proximal region including box1 and requ ires 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, t hereby indicating that the tyr residue(s) is essential for the activat ion of JNK. Mutation analyses of each tyr residue indicated that none of the tyr residues seems essential for the activation of JNK, indicat ing multiple tyr residues play a similar function to transduce signals for this activation. (C) 1997 Academic Press.