CAMP-DEPENDENT PROTEIN-KINASE ACTIVITY IS ESSENTIAL FOR PREAGGREGATIVE GENE-EXPRESSION IN DICTYOSTELIUM

Constitutive inhibition of cAMP-dependent protein kinase (PKA) in Dict yostelium cells blocks cell aggregation and development, We investigat ed the cause of the aggregation defect in transformants overexpressing dominant-negative PKA regulatory subunits (PKA-R(M)) under an actin 1 5 promoter, These mutants could not relay pulses of the chemoattractan t cAMP, due to a defect in expression of the aggregative adenylyl cycl ase (ACA) gene, Unstimulated and cAMP pulse-induced expression of othe r aggregative genes encoding the cAMP receptor cAR1, adhesive contact sites A and cAMP-phosphodiesterase were also strongly reduced in the m utants, Additionally, the expression of the discoidin I gene, that is expressed early in development in response to cell density sensing fac tors, was almost completely absent, These data are in interesting cont rast with observations that cAMP relay and aggregative gene expression are normal in null mutants for the PKA catalytic (C) subunit and sugg est the presence of multiple C subunit genes in Dictyostelium and an a lmost universal requirement for PKA activity in developmental gene exp ression.