Eukaryote-Like Serine/Threonine Kinases and Phosphatases in Bacteria

Abstract

SUMMARY Genomic studies have revealed the presence of Ser/Thr kinases and phosphatases in many bacterial species, although their physiological roles have largely been unclear. Here we review bacterial Ser/Thr kinases (eSTKs) that show homology in their catalytic domains to eukaryotic Ser/Thr kinases and their partner phosphatases (eSTPs) that are homologous to eukaryotic phosphatases. We first discuss insights into the enzymatic mechanism of eSTK activation derived from structural studies on both the ligand-binding and catalytic domains. We then turn our attention to the identified substrates of eSTKs and eSTPs for a number of species and to the implications of these findings for understanding their physiological roles in these organisms.

Protein Kinase/Phosphatase Function Correlates with Gliding Motility in Mycoplasma pneumoniae

“…Rather, we suggest that PrpC and PrkC constitute part of a regulatory circuit comparable to that in B. subtilis wherein the phosphorylation of elongation factor Tu and other phosphoproteins influences aspects of sporulation and cell wall biosynthesis (18,20). Homologous eSTP/eSTK-associated regulation of swarming in Myxococcus xanthus, cell division in Mycobacterium tuberculosis, and virulence in Yersinia pseudotuberculosis have been previously reported (19), indicating that reversible protein phosphorylation is coupled to a diverse slate of functions in bacteria. We submit that gliding motility in M. pneumoniae is a strong candidate for inclusion in the growing category of cellular processes in prokaryotes controlled in part by reversible Ser/Thr phosphorylation.…”

“…It is possible that P1 is phosphorylated by a different, unidentified protein kinase, but it is more likely that the PrkC truncation in this mutant affects the function beyond enzymatic activity. For example, the function of eSTKs such as PrkC can involve the formation of homodimers via extracellular ligand binding (19), and truncation of PrkC here might impact that aspect of activity. The comparable hyperphosphorylation and gliding phenotypes of the complemented prkC mutant and wild-type M. pneumoniae carrying a second prkC allele suggest that the truncated PrkC might form fully functional dimers when paired with full-length wild-type PrkC.…”

“…PrpC and its homologs are often partnered with the cognate kinase PrkC, a highly conserved eukaryotic-like Ser/Thr kinase (eSTK). Mutant analysis in Bacillus subtilis has shown that homologs to these enzymes regulate sporulation and cell wall development by reversible phosphorylation (18)(19)(20). Similar reversible phosphorylation might occur in M. pneumoniae, where terminal organelle proteins HMW1 and HMW2 (MPN310) are phosphorylated in an ATP-dependent manner (21).…”

The Ser/Thr protein kinase AfsK regulates polar growth and hyphal branching in the filamentous bacteria Streptomyces

“…The Actinobacteria are an ancient and deeply branching bacterial phylum in which STKs are particularly widespread and abundant. For example, Streptomyces coelicolor encodes at least 34 and Mycobacterium tuberculosis encodes 11 STKs (20,(24)(25)(26). In S. coelicolor, a recent phosphoproteomic survey detected at least 40 phosphoproteins (27), but the number of substrates is anticipated to be much larger, underlining the fundamental importance of actinobacterial STKs and the need for improved understanding of their substrates and biological functions.…”

“…However, it is now clear, for example, from genomics and phosphoproteomics, that STKs are extensively used by bacteria in a variety of regulatory roles (reviewed recently in ref. 20). For example, in B. subtilis, the STK PrkC controls germination of spores in response to muropeptides released from bacterial cell walls, and, in Streptococcus pneumoniae, the STK StkP is involved in coordination of growth and cell division (21,22).…”