It is known that cellular signals produced in response to an inappropriate spindle formation cause the cell to be arrested at metaphase (M) in the cell cycle. We report here that the 42-kDa isoform of MAPK (ERK2) was tyrosyl-phosphorylated and activated in response to epidermal growth factor (EGF) in interphase but not in M-arrested HeLa cells. However, the basal level of activity of M-arrested cells was higher than that of interphase, although the overall tyrosyl phosphorylation content was small. Further, the EGF receptor and its associated proteins GTPase-activating protein and phospholipase C were phosphorylated in M-arrested cells to a lower extent than they were in interphase. This implies that in spite of its high level of basal activity, the scarcity of MAPK activation in mitosis in response to EGF stems from an early impairment of phosphorylation of the receptor and neighboring proteins. The biological significance of these results underlies the importance of keeping the cell sheltered from extracellular signals when it undergoes division.
Enzyme Activation Epidermal Growth Factor