Protein phosphorylation on serine, threonine, and tyrosine residues modulates membrane-protein interactions and transcriptional regulation in Salmonella typhimurium.

There exists a plethora of tyrosine kinases that play essential roles in regulation of eukaryotic proteins. Several dual specificity kinases that phosphorylate proteins on threonine, serine, and tyrosine residues also play critical roles in eukaryotic phosphorylation cascades. In contrast, very few prokaryotic proteins have been shown to be phosphorylated on tyrosine residues, and the functions of the rare examples remain obscure. Furthermore, no dual specificity kinases have been described in prokaryotes. Our results indicate that PutA protein from the bacterium Salmonella typhimurium autophosphorylates on several threonine, serine, and tyrosine residues. PutA protein both represses the proline utilization (put) operon and degrades proline to glutamate. These two opposing functions are regulated by the availability of proline and the membrane sites needed for the proline dehydrogenase activity of PutA protein. In addition, these functions are modulated by phosphorylation of PutA protein. The rate of dephosphorylation of PutA protein is determined by the availability of proline and membranes. Dephosphorylated PutA protein has a higher DNA binding affinity than the phosphorylated protein and thus may prevent toxic overexpression of PutA protein in the absence of available membrane sites.