Depletion of inorganic phosphate within the cell is required for activation of the Pho regulon in most prokaryotes. In the most commonly studied bacterium, E. coli, seven total proteins are used to detect intracellular levels of inorganic phosphate along with transfusing that signal appropriately. Of the seven proteins, one is a metal binding protein (PhoU) and four are phosphate-specific transporters (Pst S, Pst C, Pst A, and Pst B). The transcriptional response regulator PhoR activates PhoB when it senses low intracellular inorganic phosphate levels.