A novel role of differentiation-inducing factor-1 in Dictyostelium development, assessed by the restoration of a developmental defect in a mutant lacking mitogen-activated protein kinase ERK2

It has been previously reported that the differentiating wild-type cells of Dictyostelium discoideum secrete a diffusible factor or factors that are a ble to rescue the developmental defect in the mutant lacking extracellular signal-regulated kinase 2 (ERK2), encoded by the gene erkB. In the present study, it is demonstrated that differentiation-inducing factor-1 (DIF-1) fo r stalk cells can mimic the role of the factor(s) and the mechanism of the action of DIF-1 in the erkB null mutant is also discussed. The mutant usual ly never forms multicellular aggregates, because of its defect in cyclic ad enosine monophosphate (cAMP) signaling. In the presence of 100 nM DIF-1, ho wever, the mutant cells formed tiny slugs, which eventually developed into small fruiting bodies. In contrast, DIF-1 never rescued the developmental a rrest of other Dictyostelium mutants lacking adenylyl cyclase A (ACA), cAMP receptors cAR1 and cAR3, heterotrimeric G-protein, the cytosolic regulator of ACA, or the catalytic subunit of cAMP-dependent protein kinase (PKA-C). Most importantly. it was found that DIF-1 did not affect the cellular cAMP level, but rather elevated the transcriptional level of pka during the dev elopment of erkB null cells. These results suggest that DIF-1 may rescue th e developmental defect in erkB null cells via the increase in PKA activity, thus giving the first conclusive evidence that DIF-1 plays a crucial role in the early events of Dictyostelium development as well as in prestalk and stalk cell induction.