Fungal Histidine Kinases

Abstract

Eukaryotic cells predominantly use serine, threonine, and tyrosine phosphorylation in various intracellular signal transduction pathways. In contrast, prokaryotic organisms employ numerous "two-component" systems, in which signaling is achieved by transferring a phosphoryl group from phosphohistidine in the "sensor kinase" component to aspartate in the "response regulator" component. In the last several years, genetic screens and genome projects have identified sensor kinases and response regulators in lower eukaryotes and plants, revealing that eukaryotic organisms also make use of His-Asp phosphotransfer in a limited number of signaling pathways. Extensive studies in yeasts have demonstrated that a variation of the two-component system, a multistep "phosphorelay," is the prevailing mechanism among distantly related yeast species. In the budding yeast Saccharomyces cerevisiae, a His-Asp-His-Asp phosphorelay transmits osmotic stress signals to a mitogen-activated protein kinase (MAPK) cascade to induce adaptive responses. A phosphorelay in the fission yeast Schizosaccharomyces pombe, analogous to the S. cerevisiae phosphorelay, is responsible for MAPK activation in response to peroxide stress.Mammalian cells do not have any two-component or phosphorelay systems, although protein histidine kinases unrelated to the sensor kinase may be involved in cellular signaling. Because some phosphorelay proteins are essential for virulence of microbial pathogens, including the yeast fungus Candida albicans, novel antibiotics targeted to phosphorelays may be effective against eukaryotic pathogens without causing host cell damage.

Advances in development of new tools for the study of phosphohistidine

“…70 Hultquist's phosphoryl transfer experiments can be used as a plausible explanation for the accumulation of τ-pHis with the decrease in π-and bis-pHis over time (Scheme 3). Phosphoryl transfer reactions (1)(2)(3)(4)(5)(6)(7)(8) suggest that the phosphoryl group of pHis can be donated to the imidazole nitrogen of His or α-N-acetyl-His. Comparison of (1) and (5), with (7) and (8) suggests that π-pHis has the more labile phosphorus nitrogen (P-N) bond compared with τ-pHis.…”

“…Cell signalling via a two component phosphorelay has also been found in yeast, 6 but such processes have not yet been observed in higher eukaryotes (for example, mammals, birds and fish). 8 The general role of pHis in prokaryotic and lower eukaryotic cells is shown in Figure 2.…”

“…His phosphorylation has been found in a number of organisms including bacteria, 5 fungi 6 and plants 7 and its major role is in cell signalling either via two component or multicomponent phosphorelay systems. Cell signalling via a two component phosphorelay has also been found in yeast, 6 but such processes have not yet been observed in higher eukaryotes (for example, mammals, birds and fish).…”

Mitogen-activated protein kinase signaling pathways of the tangerine pathotype of Alternaria alternata

“…[68][69][70] All fungal HSKs identified have both a histidine kinase and a RR domains. 63,65,71 Under normal osmolarity, the Sln1p kinase is spontaneously phosphorylated at a conserved histidine residue. The phosphate is passed down to Ypd1p and then Ssk1p or Skn7p in a pattern of His-Asp-His-Asp.…”

“…[63][64][65][66] The function of Hog1 is regulated by phosphorylation via a two-component histidine kinase (HSK)-mediated signaling pathway. 64,66,67 S. cerevisiae has a single HSK, Sln1p, which is required for osmotic adaption via an Ypd1p containing a histidine (His) phosphotransfer (HPt) domain and two response regulators (RR), Ssk1p and Skn7p.…”