Grossman:Cell Cell Signaling

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Cell-cell signaling, quorum sensing, and competence development:
B. subtilis, like many organisms, has mechanisms for sensing and responding to high cell density (quorum sensing). In B. subtilis, both the initiation of sporulation and competence development (the natural ability to bind and take up exogenous DNA) are regulated, in part, by high cell density. We have purified and characterized two different extracellular peptide signaling molecules that are produced by B. subtilis and accumulate in culture supernatant as cells grow to high density. Both peptides stimulate phosphorylation (activation) of the transcription factor, ComA. ComX pheromone is a 10 amino acid peptide with a hydrophobic modification on a tryptophan residue. The pheromone contains the C-terminal 10 amino acids from a 55 amino acid precursor. The cellular response to the pheromone requires the membrane-bound histidine protein kinase, ComP. ComP autophosphorylates and donates phosphate to the transcription factor, ComA. The competence and sporulation stimulating factor, CSF, is an unmodified pentapeptide. It corresponds to the C-terminal 5 amino acids of a 40 amino acid precursor (phrC). The cellular response to CSF requires transport back into the cell via oligopeptide permease, a member of the large family of ATP-dependent import/export systems found in both prokaryotes and eukaryotes. CSF stimulates accumulation of ComA~P and competence gene expression by inhibiting activity of the phosphatase, RapC. Thus, the two factors stimulate competence gene expression by affecting activity of a kinase and an opposing phosphatase.

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