Secondary literature sources for REC

The following references were automatically generated.

Mizutani T, Taniguchi Y, Aoki T, Hashimoto N, Honjo T
Conservation of the biochemical mechanisms of signal transduction among mammalian Notch family members.
Proc Natl Acad Sci U S A. 2001; 98: 9026-31
Display abstract
Mouse Notch1, which plays an important role in cell fate determination in development, is proteolytically processed within its transmembrane domain by unidentified gamma-secretase-like activity that depends on presenilin. To study this proteolytic event, we established a cell-free Notch cleavage assay system using the membrane fraction of fibroblast transfectants of various Notch constructs with deletion of the extracellular portion (Notch DeltaE). The cytoplasmic portion of Notch1 DeltaE was released from the membrane upon incubation at 37 degrees C, which was inhibited by the specific gamma-secretase inhibitor, MW167, or by overexpression of dominant negative presenilin1. Likewise, other members of mouse Notch family were proteolytically cleaved in a presenilin-dependent, MW167-sensitive manner in vivo as well as in the cell-free Notch DeltaE cleavage assay system. All four members of the mouse Notch family migrated to the nucleus and activated the transcription from the promoter carrying the RBP-J consensus sequences after they were released from the membrane. These results demonstrate the conserved biochemical mechanism of signal transduction among mammalian Notch family members.

Goudreau PN, Stock AM
Signal transduction in bacteria: molecular mechanisms of stimulus-response coupling.
Curr Opin Microbiol. 1998; 1: 160-9
Display abstract
In bacteria, adaptive responses to changing environmental conditions are mediated by signal transduction systems that involve modular protein domains. Despite great diversity in the integration of domains into different systems, studies of individual components have revealed molecular strategies that are widely applicable. Studies of receptors have advanced our understanding of how information is transmitted across membranes, the determination of three-dimensional structures of domains of histidine protein kinase domains and response regulator proteins has begun to reveal the molecular basis of signaling via two-component phosphoryltransfer pathways, and the description of 'eukaryotic-like' protein domains involved in bacterial signaling has emphasized the universality of intracellular signaling mechanisms.

Liu Y, Levit M, Lurz R, Surette MG, Stock JB
Receptor-mediated protein kinase activation and the mechanism of transmembrane signaling in bacterial chemotaxis.
EMBO J. 1997; 16: 7231-40
Display abstract
Chemotaxis responses of Escherichia coli and Salmonella are mediated by type I membrane receptors with N-terminal extracytoplasmic sensing domains connected by transmembrane helices to C-terminal signaling domains in the cytoplasm. Receptor signaling involves regulation of an associated protein kinase, CheA. Here we show that kinase activation by a soluble signaling domain construct involves the formation of a large complex, with approximately 14 receptor signaling domains per CheA dimer. Electron microscopic examination of these active complexes indicates a well defined bundle composed of numerous receptor filaments. Our findings suggest a mechanism for transmembrane signaling whereby stimulus-induced changes in lateral packing interactions within an array of receptor-sensing domains at the cell surface perturb an equilibrium between active and inactive receptor-kinase complexes within the cytoplasm.

Johnston LH, Morgan BA, Bouquin N
A yeast transcription factor activating G1 cyclin expression has similarity to bacterial signal transduction proteins.
Biochem Soc Trans. 1996; 24: 49-54

Barak R, Eisenbach M
Regulation of interaction between signaling protein CheY and flagellar motor during bacterial chemotaxis.
Curr Top Cell Regul. 1996; 34: 137-58

Blat Y, Eisenbach M
Conserved C-terminus of the phosphatase CheZ is a binding domain for the chemotactic response regulator CheY.
Biochemistry. 1996; 35: 5679-83
Display abstract
CheZ is the phosphatase of the chemotactic response regulator, CheY. There are three conserved domains on CheZ. Here we determined the function of the C-terminal domain (residues 202-214). A truncated form of CheZ, missing residues 202-214, hardly bound to the phosphorylated form of CheY. Conversely, a peptide composed of the last 19 amino acid residues of the CheZ (residues 196-214), generated by tryptic digestion, bound specifically to the phosphorylated form of CheY. This was demonstrated by both fluorescence depolarization of the peptide (labeled with fluorescein) and cross-linking. It is concluded that the conserved C-terminus of CheZ functions as a CheY-binding domain.

Swanson RV, Lowry DF, Matsumura P, McEvoy MM, Simon MI, Dahlquist FW
Localized perturbations in CheY structure monitored by NMR identify a CheA binding interface.
Nat Struct Biol. 1995; 2: 906-10
Display abstract
Phosphotransfer between the autophosphorylating histidine kinase CheA and the response regulator CheY represents a crucial step in the bacterial chemotaxis signal transduction pathway. The 15N-1H correlation spectrum of CheY complexed with an amino-terminal fragment of CheA exhibits specific localized differences in chemical shifts when compared to the spectrum of uncomplexed CheY. When mapped onto the three-dimensional structure of CheY, these changes define a region distinct from the active site. A single amino-acid substitution within this binding region on CheY, alanine to valine at position 103, significantly decreases the affinity of CheY for CheA. The binding face described by these changes partially overlaps a flagellar switch binding surface previously defined by mutagenesis.

Morrison TB, Parkinson JS
Liberation of an interaction domain from the phosphotransfer region of CheA, a signaling kinase of Escherichia coli.
Proc Natl Acad Sci U S A. 1994; 91: 5485-9
Display abstract
The CheA protein of Escherichia coli is a histidine autokinase that donates its phosphate groups to two target proteins, CheY and CheB, to regulate flagellar rotation and sensory adaptation during chemotactic responses. The amino-terminal third of CheA contains the autophosphorylation site, determinants needed to interact with the catalytic center of the molecule, and determinants needed for specific recognition of its phosphorylation targets. To understand the structural basis for these activities, we examined the domain organization of the CheA phosphotransfer region by using DNA sequence analysis, limited proteolytic digestion, and a genetic technique called domain liberation. Comparison of the functionally interchangeable CheA proteins of E. coli and Salmonella typhimurium revealed two extensively mismatched segments within the phosphotransfer region, 22 and 25 aa long, with sequences characteristic of domain linkers. Both segments were readily susceptible to proteases, implying that they have an extended, flexible structure. In contrast, the intervening segments of the phosphotransfer region, designated P1 and P2 (roughly 140 and 65 aa, respectively), were relatively insensitive, suggesting they correspond to more compactly folded structural domains. Their functional properties were explored by identifying portions of the cheA coding region capable of interfering with chemotactic behavior when "liberated" and expressed as polypeptides. P1 fragments were not inhibitory, but P2 fragments blocked the interaction of CheY with the rotational switch at the flagellar motor, leading to incessant forward swimming. These results suggest that P2 contains CheY-binding determinants which are normally responsible for phosphotransfer specificity. Domain-liberation approaches should prove generally useful for analyzing multidomain proteins and their interaction targets.

Lowry DF et al.
Signal transduction in chemotaxis. A propagating conformation change upon phosphorylation of CheY.
J Biol Chem. 1994; 269: 26358-62
Display abstract
The CheY protein from Escherichia coli and Salmonella typhimurium are among the best characterized proteins of the receiver domain family of two component signal transduction systems in bacteria. Phosphorylation of CheY plays a central role in bacterial chemotaxis. However, it is not entirely clear how its state of phosphorylation contributes to its function. Genetic evidence suggests that CheY changes its conformation upon phosphorylation. We present evidence for this conformation change by comparing the NMR 15N-1H correlation spectra of CheY.Mg2+ complex and phospho-CheY in the presence of magnesium. Large changes in chemical shift are used as indicators of chemical changes and probable structural changes in the protein backbone. Our observations suggest that significant structural changes occur in CheY upon phosphorylation and that these changes are distinct from the changes produced by magnesium ion binding. In addition to residues Asn-59 and Gly-65 that are immediately adjacent to the site of phosphorylation at Asp-57, a large number of other residues show significant chemical shift changes as a result of phosphorylation. These include Met-17, Val-21, Asn-23, Gly-39, Met-60, Met-63, Asp-64, Leu-66, Glu-67, Leu-68, Leu-69, Met-85, Val-86, Thr-87, Ala-88, Asn-94, Val-107, Lys-109, Thr-112, Ala-113, Ala-114, and Asn-121. These results appear inconsistent with the recent suggestion that phosphorylation produces the same structural changes as magnesium binding (Bellsolell, L., Prieto, J., Serrano, L., and Coll, M. (1994) J. Mol. Biol. 238, 489-495). We find that some regions change overlap with a genetically defined motor binding face. We therefore propose that the conformation switch modulates the interaction of CheY with its target, the flagellar motor. Other regions also change, possibly reflecting the many different functions of CheY homologues.

Stock J, Surette M
Bacterial chemotaxis. The motor connection.
Curr Biol. 1994; 4: 143-4
Display abstract
In bacterial chemotaxis, membrane receptors control the phosphorylation of the response regulator CheY; phospho-CheY has been found to control motility by binding to a switching apparatus attached to the flagellar motor.

Bellsolell L, Prieto J, Serrano L, Coll M
Magnesium binding to the bacterial chemotaxis protein CheY results in large conformational changes involving its functional surface.
J Mol Biol. 1994; 238: 489-95
Display abstract
The three-dimensional crystal structure of the bacterial chemotaxis protein CheY with the essential Mg2+ cation bound to the active site reveals large conformational changes caused by the metal binding. Displacements of up to 10 A are observed in several residues at the N terminus of alpha-helix 4 and in the preceding loop. One turn of this helix unwinds, and an Asn residue that was located inside the helix becomes the new N-cap. This supports the important role that N or C-cap residues play in alpha-helix stability. In addition the preceding beta-strand becomes elongated and a new beta-turn appears. The final effect is a significant modification of the surface relief of the protein in a region previously indicated, by genetic analysis, to be essential for CheY function. It is suggested that binding of a divalent cation to CheY could play a significant part in CheY activation and consequently in signal transduction in prokaryotes.

Russo FD, Slauch JM, Silhavy TJ
Mutations that affect separate functions of OmpR the phosphorylated regulator of porin transcription in Escherichia coli.
J Mol Biol. 1993; 231: 261-73
Display abstract
OmpR is a member of a family of bacterial transcriptional regulators whose activity is controlled by phosphorylation. It regulates the transcription of two genes, serving as an activator of ompC, and as both an activator and a repressor of ompF. A previously isolated collection of ompR mutations was analyzed for the effect of each on the expression of both genes simultaneously. The results of this analysis indicate that the activation, repression, and DNA binding functions of OmpR can be disrupted independently, and that mutations interfering with each of these functions cluster within the sequence of the OmpR protein. The nature of these mutations is discussed in terms of the mechanisms by which OmpR regulates transcription, and potentially similar mechanisms operating within closely related response regulators.

Stock AM et al.
Structure of the Mg(2+)-bound form of CheY and mechanism of phosphoryl transfer in bacterial chemotaxis.
Biochemistry. 1993; 32: 13375-80
Display abstract
The response regulator protein of bacterial chemotaxis, CheY, is representative of a large family of signal transduction proteins that function as phosphorylation-activated switches to regulate the activities of associated effector domains. These regulators catalyze the metal ion-dependent phosphoryl transfer and dephosphorylation reactions that control the effector activities. The crystal structures of Salmonella typhimurium CheY with and without Mg2+ bound at the active site have been determined and refined at 1.8-A resolution. While the overall structures of metal-bound and metal-free CheY are similar, significant rearrangements occur within the active site involving the three most highly conserved residues of the response regulator family. Conservation of the cluster of carboxylate side chains at the active site of response regulator domains can be rationalized in terms of their role in coordinating the catalytically essential divalent metal ion. The Mg2+ coordination geometry provides insights to the mechanism of phosphoryl transfer.

Kadner RJ, Webber CA, Island MD
The family of organo-phosphate transport proteins includes a transmembrane regulatory protein.
J Bioenerg Biomembr. 1993; 25: 637-45
Display abstract
This review article briefly summarizes aspects of our current understanding of the Uhp sugar phosphate transport system in enteric bacteria, particularly the mode of genetic regulation of its synthesis. This regulation occurs by a process that involves an example of the very widespread and ever-growing group of so-called two-component bacterial regulatory systems, a mechanism of response to environmental signals that employs phosphate transfer reactions between constituent proteins. Of emphasis here is the unusual involvement in transmembrane signaling of the UhpC protein which is related in sequence and structure to some transport proteins, including the very protein whose synthesis it helps regulate.

Stock JB, Surette MG, McCleary WR, Stock AM
Signal transduction in bacterial chemotaxis.
J Biol Chem. 1992; 267: 19753-6

Stock JB, Lukat GS, Stock AM
Bacterial chemotaxis and the molecular logic of intracellular signal transduction networks.
Annu Rev Biophys Biophys Chem. 1991; 20: 109-36

Helmann JD, Shewchuk LM, Walsh CT
Regulation of gene expression by mercury.
Adv Inorg Biochem. 1990; 8: 33-61

Timme TL, Lawrence CB, Moses RE
Two new members of the OmpR superfamily detected by homology to a sensor-binding core domain.
J Mol Evol. 1989; 28: 545-52
Display abstract
The OmpR superfamily includes proteins that act as transcriptional regulators of operons that respond to environmental stimuli. A homologous domain near the N-terminus, termed a sensor-binding core domain, is thought to play a role in recognition of a signal transduction protein. We have identified two previously unrecognized members of this regulator family of proteins: a 23.8-kd protein transcribed from the uvrC transcription unit and the PgtA gene product, which is a phosphoglycerate transport regulatory protein. The sensor-binding core domain is also present in four proteins that regulate bacterial sporulation and chemotaxis. The 23.8-kd protein also has sequence similarity to elongation factor Tu and two regulatory proteins: HtpR, the heat-shock regulatory protein, and TraJ, a regulator of expression of genes involved in conjugation. There is a 77-amino acid region near the C-terminus of the 23.8-kd protein that has 30% similarity with a 28.1-kd protein coded for by an open reading frame 5' to the reading frame of the 23.8-kd protein in the uvrC transcription unit. Genetic distance analysis of amino acid sequences of proteins with a sensor-binding core domain suggests that the 23.8-kd protein and the chemotaxis regulatory proteins are distantly related to the other regulatory proteins in the OmpR superfamily.

Sanders DA, Gillece-Castro BL, Stock AM, Burlingame AL, Koshland DE Jr
Identification of the site of phosphorylation of the chemotaxis response regulator protein, CheY.
J Biol Chem. 1989; 264: 21770-8
Display abstract
The protein (Escherichia coli CheY) that controls the direction of flagellar rotation during bacterial chemotaxis has been shown to be phosphorylated on the aspartate 57 residue. The residue phosphorylated is present within a conserved sequence in every member of a family of bacterial regulatory proteins. The phosphorylation is transient, with a much shorter half-life than that expected of a simple acyl phosphate intermediate, indicating that the sequence and conformation of the protein is designed to achieve a rapid hydrolysis. The CheY-phosphate linkage can be reductively cleaved by sodium borohydride. High-performance tandem mass-spectrometric analysis of proteolytic peptides derived from [3H]borohydride-reduced phosphorylated CheY protein was used to identify the position of phosphorylation. Mutants with altered aspartate 57 exhibited no chemotaxis. When aspartate 13, another conserved residue, was changed, greatly reduced chemotaxis was observed, suggesting an important role for aspartate 13. The rate-determining step of chemotactic signaling is governed by the kinetics of formation and hydrolysis of the CheY protein phosphoaspartate bond. The CheY protein apparently functions as a protein phosphatase that possesses a transient covalent intermediate. Transient phosphorylation of an aspartate residue is an effective mechanism for producing a biochemical signal with a short concentration-independent half-life. The duration of the signal can be controlled by small structural elements within the phosphorylated protein.

Stock A, Chen T, Welsh D, Stock J
CheA protein, a central regulator of bacterial chemotaxis, belongs to a family of proteins that control gene expression in response to changing environmental conditions.
Proc Natl Acad Sci U S A. 1988; 85: 1403-7
Display abstract
During bacterial chemotaxis, the binding of stimulatory ligands to chemoreceptors at the cell periphery leads to a response at the flagellar motor. Three proteins appear to be required for receptor-mediated control of swimming behavior, the products of the cheA, cheW, and cheY genes. Here we present the complete nucleotide sequence of the Salmonella typhimurium cheA gene together with the purification and characterization of its protein product. The protein is a 73,000 Mr cytoplasmic constituent. Amino acid-sequence comparisons indicate that it belongs to a family of bacterial regulatory proteins including the products of the cpxA, dctB, envZ, ntrB, phoR, phoM, and virA genes. Each member of this family has a conserved domain of approximately equal to 200 residues within its C terminus. We have previously shown that another chemotaxis protein, CheY, represents a domain of protein structure that has been conserved within a second large family of bacterial regulatory proteins. Each protein of the CheA family seems to function as a regulator of a different CheY homologue. Although each pair of proteins appears to produce a specialized response to a distinct type of stimulus, the relationships in primary structure suggest that a similar molecular mechanism may be involved.