Protein phosphorylation and regulation of adaptive responses in bacteria involve histidine protein kinases (HPK) and their associated response regulators (RR). These proteins facilitate signal transduction through the transfer of phosphoryl groups from ATP to histidine residues in HPK, then to aspartic acid residues in RR, and finally to water. This phosphorylation process controls the activity of response regulators, which in turn regulate adaptive responses. The study highlights the importance of phosphorylation in bacterial signal transduction, particularly in systems such as chemotaxis, nitrogen regulation, phosphate regulation, and osmoregulation. The homologous families of HPK and RR are found in various bacteria, including gram-negative and gram-positive species. The structure and function of these proteins are discussed, along with their roles in different adaptive responses. The review also addresses the cross-talk between parallel signal transduction pathways and the global regulation of cell function. The study emphasizes the conserved phosphotransfer enzymology and the importance of phosphorylation in bacterial adaptation to environmental signals.Protein phosphorylation and regulation of adaptive responses in bacteria involve histidine protein kinases (HPK) and their associated response regulators (RR). These proteins facilitate signal transduction through the transfer of phosphoryl groups from ATP to histidine residues in HPK, then to aspartic acid residues in RR, and finally to water. This phosphorylation process controls the activity of response regulators, which in turn regulate adaptive responses. The study highlights the importance of phosphorylation in bacterial signal transduction, particularly in systems such as chemotaxis, nitrogen regulation, phosphate regulation, and osmoregulation. The homologous families of HPK and RR are found in various bacteria, including gram-negative and gram-positive species. The structure and function of these proteins are discussed, along with their roles in different adaptive responses. The review also addresses the cross-talk between parallel signal transduction pathways and the global regulation of cell function. The study emphasizes the conserved phosphotransfer enzymology and the importance of phosphorylation in bacterial adaptation to environmental signals.