Figure 1

The PKA-regulatory pathway. Biochemical, genetic and physiological data were used to describe a pathway that regulates PKA during Dictyostelium development. Gene expression data were not considered in the construction of this network. PufA is an RNA-binding protein that sequesters pkaC mRNA and prevents its translation. YakA is a protein kinase that indirectly inhibits PufA activity. PkaC catalytic activity is inhibited by the regulatory subunit PkaR. An extracellular cAMP signal is integrated through various cAMP receptors (Car), which result in the activation of the aggregative adenylyl cyclase AcaA. AcaA activation leads to production of cAMP, which binds PkaR and ends the inhibition of PkaC. Two proteins that contain response regulator domains control PkaR. The adenylyl cyclase AcrA functions after the aggregation stage of development and produces cAMP, and the cAMP-phosphodiesterase RegA degrades intracellular cAMP. These two response regulator proteins are regulated indirectly by histidine kinases (Dhk). The components that function downstream of PkaC are unknown (?). Nodes in the graph represent genes and edges represent regulatory relationships: positive (arrows) and negative (barred lines). Dashed lines indicate indirect interactions. The proteins in black are encoded by genes used in our analysis.