DIFFERENTIATION STAGE SPECIFICITY OF TYROSINE PHOSPHORYLATION IN RESPONSE TO GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR (GM-CSF)

We have previously described differentiation associated tyrosine protein kinase activity in WEHI-3B monomyelocytic leukemia cells and have presented evidence which suggests that this activity may not be involved in the initiation of the differentiation process, but more likely has a functional role in the mature myeloid cell. The present study was undertaken in an attempt to identify the protein(s) responsible for the tyrosine protein kinase activity and to seek a potential role for this activity in the mature cell. We and others have detected the p92c-fes tyrosine protein kinase in WEHI-3B cells. This protein has been implicated in myeloid differentiation, as well as in the transduction of signals in response to granulocyte macrophage colony stimulating factor (GM-CSF). Thus, it was of interest to determine whether tyrosine phosphorylation may be involved in the response of WEHI-3B cells to GM-CSF. Treatment of differentiated WEHI-3B D+ cells with GM-CSF was found to result in the tyrosine phosphorylation of a number of endogenous cellular proteins in a concentration-dependent, rapid and transient manner. In contrast, the cytokine did not elicit such a response in undifferentiated cells, despite the fact that undifferentiated cells have been reported to possess GM-CSF receptors. These findings are consistent with the concept that the effects of GM-CSF on differentiated myeloid cells are mediated through tyrosine phosphorylation, that only differentiated cells are competent to accomplish this event, and that this response constitutes at least one functional role for the myeloid differentiation associated tyrosine protein kinase activity.