The serine, threonine, and/or tyrosine-specific protein kinases and protein phosphatases of prokaryotic organisms: a family portrait

Abstract

Inspection of the genomes for the bacteria Bacillus subtilis 168, Borrelia burgdorferi B31, Escherichia coli K-12, Haemophilus influenzae KW20, Helicobacter pylori 26695, Mycoplasma genitalium G-37, and Synechocystis sp PCC 6803 and for the archaeons Archaeoglobus fulgidus VC-16 DSM4304, Methanobacterium thermoautotrophicum delta H, and Methanococcus jannaschii DSM2661 revealed that each contains at least one ORF whose predicted product displays sequence features characteristic of eukaryote-like protein-serine/threonine/tyrosine kinases and protein-serine/threonine/tyrosine phosphatases. Orthologs for all four major protein phosphatase families (PPP, PPM, conventional PTP, and low molecular weight PTP) were present in the bacteria surveyed, but not all strains contained all types. The three archaeons surveyed lacked recognizable homologs of the PPM family of eukaryotic protein-serine/threonine phosphatases; and only two prokaryotes were found to contain ORFs for potential phosphatases from all four major families. Intriguingly, our searches revealed a potential ancestral link between the catalytic subunits of microbial arsenate reductases and the protein-tyrosine phosphatases; they share similar ligands (arsenate versus phosphate) and features of their catalytic mechanism (formation of arseno-versus phospho-cysteinyl intermediates). It appears that all prokaryotic organisms, at one time, contained the genetic information necessary to construct protein phosphorylation-dephosphorylation networks that target serine, threonine, and/or tyrosine residues on proteins. However, the potential for functional redundancy among the four protein phosphatase families has led many prokaryotic organisms to discard one, two, or three of the four.

A PP2C-type phosphatase dephosphorylates the PII signaling protein in the cyanobacterium Synechocystis PCC 6803

“…34). By contrast, the similarity to the eukaryotic PP2C homologues and to the previously characterized B. subtilis PP2C homologues SpoIIE (8) and relatives is restricted to highly conserved signature sequences (4). A phylogenetic tree of the Synechocystis PP2C-homologues was constructed, which shows that most of these (the products of slr0114, slr1860, slr1983, slr2031, and sll1365) belong to the SpoIIE-class of PP2C-homologues, whereas pphA is a member of the bacterial PP2C-phosphatases, designated ''group I'' in ref.…”

“…The deduced gene product of pphA contains 254 aa, comprising a polypeptide with a calculated molecular mass of 28.3 kDa. This size corresponds to that of the catalytic domain of PP2C phosphatases, with its 11 conserved motifs (22) scattered over the PphA sequence (4). A BLASTP homology search revealed the highest degree of amino acid identity with hypothetical proteins from other cyanobacterial genomes (Anabaena sp.…”

“…From this it appears that pphA is transcribed monocistronically from a promoter, which is located within the 3Ј end of the preceding ORF sll1770. Interestingly, the predicted sll1770 product has been described as a putative protein kinase in a search for ''eukaryote-like'' protein serine͞ threonine kinases in prokaryotes (4). To test whether the sll1770 product may be a PII kinase, a mutant was created in which this gene was disrupted (Fig.…”

“…During the past years, it has become increasingly evident that in addition to this signaling mode, protein O-phosphorylation, previously thought to be only important in eukaryotic signal transduction, occurs in various groups of Gram-negative and Gram-positive bacteria (2,3) and is particularly widespread in cyanobacteria (4). Surveys of the 3.6-Mbp genome of Synechocystis PCC 6803 revealed more than 20 putative serine͞threonine and tyrosine-specific protein kinases (PK) and protein phosphatases (PP) (4,5).…”

“…On a structural basis, they comprise two superfamilies, the large PPP superfamily with phosphatases PP1, PP2A, and PP2B and the smaller PPM superfamily with the Mg 2ϩ ͞Mn 2ϩ -dependent protein phosphatase 2C (PP2C) family, characterized by 11 conserved signature motifs in the catalytic domain (21,22). Previous inspections of the Synechocystis PCC 6803 genome revealed eight genes for prospective members of the PP2C family, but only one for a putative PPP-type phosphatase (4,5). Because Synechocystis PCC 6803 possesses a highly This paper was submitted directly (Track II) to the PNAS office.…”