Transmembrane Signaling and the Regulation of Histidine Kinase Activity

Transmembrane signal transduction plays a central role in biology. All cells transport information from surface receptors into the cytoplasm where it is processed and used to regulate virtually every aspect of biological activity. This is analogous to the uptake of nutrient molecules from the environment. In the case of membrane transporters and channels, the molecular basis for their function has become clear through high-resolution structural studies. This chapter focuses on functions of histidine protein kinase (HPK) and HPK-linked receptors in well-characterized prokaryotic systems that regulate gene expression and motility. In prokaryotes, histidine protein kinases (HPKs) transduce sensory inputs into protein phosphorylation outputs. Although all HPKs share homologous kinase catalytic domains, their activities are generally regulated by external stimuli via a wide variety of sensory input domains. Like tyrosine protein kinases, dimerization is important for HPK function. A possible insight into the mechanism of signaling by HPKs comes from observations of tight clustering by the chemotaxis receptors in Escherichia coli and other bacteria. The examination of the E. coli chemotaxis system reveals that changes in lateral interaction among hundreds or even thousands of receptors in large clusters play a key role in chemotaxis signal transduction.