Signal transduction is a ubiquitous mechanism responsible for cell adaptation to environmental changes in both prokaryotes and eukaryotes. Cellular responses to the dynamic changes in the environment are mediated by a cascade of events involving protein kinases, which activate protein substrates by ATP-dependent phosphorylation on specific residues such as histidine and aspartate in prokaryotes (two-component systems) and serine/threonine, or tyrosine in eukaryotic or eukaryotic-like protein kinases. The reverse regulation of kinases (dephosphorylation) is mediated by protein phosphatases. Protein phosphatases participate in modulating a variety of cellular events such as metabolism, gene transcription, cell cycle control, immune response, and cell growth, etc. In addition, protein phosphatases have also been associated with virulence contributing to the intracellular survival of pathogens. For example, the tyrosine phosphatase YopH of Yersinia pseudotuberculosis dephosphorylates host proteins, the tyrosine phosphatase SptP from Salmonella typhimurium, which is translocated into the host, causes a disorganization of the actin cytoskeleton, while Stp, a serine/threonine phosphatase from Listeria monocytogenes dephosphorylates the host elongation factor EF-Tu.

Signal transduction in Mycobacterium avium spp. paratuberculosis (Map) is regulated according to the annotated genome by twelve two-component systems based on signal-transducing histidine kinases, nine serine/threonine protein kinases, five proteins containing serine/threonine kinase catalytic domains, and two tyrosine phosphatases. Interestingly, the annotated genome does not possess a defined tyrosine kinase, suggesting that both proteins might act in the host upon infection. Recently, we have reported that map1985 is a functional low-molecular tyrosine phosphatase, which is secreted intracellularly upon macrophage infection. Then, interfering with the host signal transduction could contribute to the pathogen survival in macrophages.