Attenuation of sensory receptor signaling by covalent modification.
The Tar receptor is a transmembrane protein that regulates bacterial chemotaxis in response to changes in the level of aspartic acid in the medium. The extracellular portion of the protein can bind aspartate, and the cytoplasmic portion modulates CheA kinase activity. The receptor can either activate or inhibit the kinase. The cytoplasmic portion of the receptor can be modified by carboxymethylation of specific glutamic acid residues. To test the effects of differential methylation on receptor function, we prepared membranes from cells that have specifically modified forms of the receptor and tested the relative ability of each of these forms to activate or inhibit CheA kinase. Completely demethylated receptor was a potent inhibitor and poor activator of the kinase, while the fully modified receptor was an excellent activator but an inefficient inhibitor. Partially modified receptor could act both as an effective inhibitor and as an activator. Reversible modification provides a mechanism that allows the cell to accumulate a population of receptor molecules capable of generating a wide range of signaling intensities.
Borkovich
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Division of Biology, California Institute of Technology, Pasadena 91125.
Alex
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Simon
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D000595:Amino Acid Sequence; D001224:Aspartic Acid / Q000378:metabolism / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D002628:Chemoreceptor Cells; D002630:Chemotactic Factors / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins; D000071677:Histidine Kinase; D007700:Kinetics; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D000072236:Methyl-Accepting Chemotaxis Proteins; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D011956:Receptors, Cell Surface; D015398:Signal Transduction
D001426:Bacterial Proteins; D002630:Chemotactic Factors; D029968:Escherichia coli Proteins; D008565:Membrane Proteins; D000072236:Methyl-Accepting Chemotaxis Proteins; D011956:Receptors, Cell Surface; C057331:Tar protein, E coli; D001224:Aspartic Acid; D011494:Protein Kinases; D000071677:Histidine Kinase; C000607608:cheA protein, E coli