Alexander J Ninfa

Summary

Affiliation: University of Michigan
Country: USA

Publications

  1. pmc Regulation of carbon and nitrogen metabolism: adding regulation of ion channels and another second messenger to the mix
    Alexander J Ninfa
    Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI 48109, USA
    Proc Natl Acad Sci U S A 104:4243-4. 2007
  2. pmc Use of two-component signal transduction systems in the construction of synthetic genetic networks
    Alexander J Ninfa
    Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI 48109 0606, USA
    Curr Opin Microbiol 13:240-5. 2010
  3. ncbi request reprint PII signal transduction proteins
    A J Ninfa
    Dept of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI 48109 0606, USA
    Trends Microbiol 8:172-9. 2000
  4. ncbi request reprint Hysteresis vs. graded responses: the connections make all the difference
    Alexander J Ninfa
    Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI 48109 0606, USA
    Sci STKE 2004:pe20. 2004
  5. pmc Regulation of autophosphorylation of Escherichia coli nitrogen regulator II by the PII signal transduction protein
    P Jiang
    Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan
    J Bacteriol 181:1906-11. 1999
  6. ncbi request reprint PII signal transduction proteins: sensors of alpha-ketoglutarate that regulate nitrogen metabolism
    Alexander J Ninfa
    Department of Biological Chemistry, University of Michigan Medical School, 1301 E Catherine St, Ann Arbor, Michigan 48109 0606, USA
    Curr Opin Microbiol 8:168-73. 2005
  7. pmc Sensation and signaling of alpha-ketoglutarate and adenylylate energy charge by the Escherichia coli PII signal transduction protein require cooperation of the three ligand-binding sites within the PII trimer
    Peng Jiang
    Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109 0606, USA
    Biochemistry 48:11522-31. 2009
  8. pmc Mutations altering the N-terminal receiver domain of NRI (NtrC) That prevent dephosphorylation by the NRII-PII complex in Escherichia coli
    Augen A Pioszak
    Department of Biological Chemistry, University of Michigan Medical School, 1301 E Catherine, Ann Arbor, MI 48109 0606, USA
    J Bacteriol 186:5730-40. 2004
  9. pmc Alpha-ketoglutarate controls the ability of the Escherichia coli PII signal transduction protein to regulate the activities of NRII (NrB but does not control the binding of PII to NRII
    Peng Jiang
    Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109 0606, USA
    Biochemistry 48:11514-21. 2009
  10. ncbi request reprint Physiological role of the GlnK signal transduction protein of Escherichia coli: survival of nitrogen starvation
    Timothy A Blauwkamp
    Department of Biological Chemistry, University of Michigan Medical School, 1301 E Catherine, Ann Arbor, MI 48109 0606, USA
    Mol Microbiol 46:203-14. 2002

Collaborators

Detail Information

Publications46

  1. pmc Regulation of carbon and nitrogen metabolism: adding regulation of ion channels and another second messenger to the mix
    Alexander J Ninfa
    Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI 48109, USA
    Proc Natl Acad Sci U S A 104:4243-4. 2007
  2. pmc Use of two-component signal transduction systems in the construction of synthetic genetic networks
    Alexander J Ninfa
    Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI 48109 0606, USA
    Curr Opin Microbiol 13:240-5. 2010
    ..Recent successes in this area are noted, such as the development of light-sensitive transmitter proteins and chemotactic receptors responsive to nitrate...
  3. ncbi request reprint PII signal transduction proteins
    A J Ninfa
    Dept of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI 48109 0606, USA
    Trends Microbiol 8:172-9. 2000
    ....
  4. ncbi request reprint Hysteresis vs. graded responses: the connections make all the difference
    Alexander J Ninfa
    Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI 48109 0606, USA
    Sci STKE 2004:pe20. 2004
    ..Finally, bistability can result in enzymatic systems in which multiple reversible covalent modifications occur, even when no overt feedback loops are present...
  5. pmc Regulation of autophosphorylation of Escherichia coli nitrogen regulator II by the PII signal transduction protein
    P Jiang
    Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan
    J Bacteriol 181:1906-11. 1999
    ....
  6. ncbi request reprint PII signal transduction proteins: sensors of alpha-ketoglutarate that regulate nitrogen metabolism
    Alexander J Ninfa
    Department of Biological Chemistry, University of Michigan Medical School, 1301 E Catherine St, Ann Arbor, Michigan 48109 0606, USA
    Curr Opin Microbiol 8:168-73. 2005
    ..The protein family shows high conservation, with examples in eukaryota (plants and eukaryotic algae), archaea, and bacteria. This distribution indicates that PII is one of the most ancient signalling proteins known...
  7. pmc Sensation and signaling of alpha-ketoglutarate and adenylylate energy charge by the Escherichia coli PII signal transduction protein require cooperation of the three ligand-binding sites within the PII trimer
    Peng Jiang
    Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109 0606, USA
    Biochemistry 48:11522-31. 2009
    ....
  8. pmc Mutations altering the N-terminal receiver domain of NRI (NtrC) That prevent dephosphorylation by the NRII-PII complex in Escherichia coli
    Augen A Pioszak
    Department of Biological Chemistry, University of Michigan Medical School, 1301 E Catherine, Ann Arbor, MI 48109 0606, USA
    J Bacteriol 186:5730-40. 2004
    ..The properties of these altered proteins are consistent with the hypothesis that the NRII-PII complex is not a true phosphatase but rather collaborates with NRI approximately P to bring about its dephosphorylation...
  9. pmc Alpha-ketoglutarate controls the ability of the Escherichia coli PII signal transduction protein to regulate the activities of NRII (NrB but does not control the binding of PII to NRII
    Peng Jiang
    Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109 0606, USA
    Biochemistry 48:11514-21. 2009
    ..Thus, PII control of NRII activities could be dissected into distinct binding and regulation steps, and when present in its physiological concentration range, alpha-ketoglutarate apparently played a role in only the latter step...
  10. ncbi request reprint Physiological role of the GlnK signal transduction protein of Escherichia coli: survival of nitrogen starvation
    Timothy A Blauwkamp
    Department of Biological Chemistry, University of Michigan Medical School, 1301 E Catherine, Ann Arbor, MI 48109 0606, USA
    Mol Microbiol 46:203-14. 2002
    ..The specific roles of GlnK during nitrogen starvation were not the result of a distinct function of the protein, as expression of PII from the glnK promoter in cells lacking GlnK restored the wild-type phenotypes...
  11. doi request reprint Characterization of the Reconstituted UTase/UR-PII-NRII-NRI Bicyclic Signal Transduction System that Controls the Transcription of Nitrogen-Regulated (Ntr) Genes in Escherichia coli
    Peng Jiang
    Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109 0606, United States
    Biochemistry 51:9045-57. 2012
    ....
  12. pmc Activation of the glnA, glnK, and nac promoters as Escherichia coli undergoes the transition from nitrogen excess growth to nitrogen starvation
    Mariette R Atkinson
    Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
    J Bacteriol 184:5358-63. 2002
    ..coli was grown on a low concentration of ammonia in combination with arginine as a nitrogen source, consistent with the hypothesis that Ntr genes other than glnA become activated only upon amplification of the NRI concentration...
  13. ncbi request reprint Governor of the glnAp2 promoter of Escherichia coli
    Mariette R Atkinson
    Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI 48109 0606, USA
    Mol Microbiol 46:1247-57. 2002
    ....
  14. pmc Context-dependent functions of the PII and GlnK signal transduction proteins in Escherichia coli
    Mariette R Atkinson
    Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109 0606, USA
    J Bacteriol 184:5364-75. 2002
    ..In addition, we describe results suggesting that an additional, unknown mechanism may control the cellular level of GlnK...
  15. pmc Reconstitution of Escherichia coli glutamine synthetase adenylyltransferase from N-terminal and C-terminal fragments of the enzyme
    Peng Jiang
    Department of Biological Chemistry, University of Michigan Medical Center, Ann Arbor, Michigan 48109 0606, USA
    Biochemistry 48:415-23. 2009
    ..Finally, our results are consistent with the hypothesis that the AR activity of the N-terminal domain required activation by the opposing C-terminal (AT) domain...
  16. doi request reprint A source of ultrasensitivity in the glutamine response of the bicyclic cascade system controlling glutamine synthetase adenylylation state and activity in Escherichia coli
    Peng Jiang
    Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109, United States
    Biochemistry 50:10929-40. 2011
    ..Our results suggest that the AT activity is only bound and activated by completely unmodified PII and that this design is largely responsible for ultrasensitivity of the bicyclic system...
  17. ncbi request reprint Mechanism of the PII-activated phosphatase activity of Escherichia coli NRII (NtrB): how the different domains of NRII collaborate to act as a phosphatase
    Augen A Pioszak
    Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109 0606, USA
    Biochemistry 42:8885-99. 2003
    ....
  18. ncbi request reprint Escherichia coli glutamine synthetase adenylyltransferase (ATase, EC 2.7.7.49): kinetic characterization of regulation by PII, PII-UMP, glutamine, and alpha-ketoglutarate
    Peng Jiang
    Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109 0606, USA
    Biochemistry 46:4133-46. 2007
    ..Rather, alpha-ketoglutarate dramatically affected the extent of activation or inhibition of the enzyme by PII or PII-UMP. A working hypothesis for the regulation of the AT and AR activities, consistent with all data, is presented...
  19. ncbi request reprint Crystal structure of the C-terminal domain of the two-component system transmitter protein nitrogen regulator II (NRII; NtrB), regulator of nitrogen assimilation in Escherichia coli
    Yuanda Song
    Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109 0606, USA
    Biochemistry 43:6670-8. 2004
    ..This unique structural element in the NRII C-terminal domain may play a role in binding PII or in intramolecular signal transduction...
  20. ncbi request reprint Development of genetic circuitry exhibiting toggle switch or oscillatory behavior in Escherichia coli
    Mariette R Atkinson
    Department of Biological Chemistry, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA
    Cell 113:597-607. 2003
    ..For the toggle switch, LacI was provided constitutively; the level of active repressor was controlled by using a lacY mutant and varying the concentration of IPTG. This circuitry provided nearly discontinuous expression of activator...
  21. ncbi request reprint Antagonism of PII signalling by the AmtB protein of Escherichia coli
    Timothy A Blauwkamp
    Department of Biological Chemistry, University of Michigan Medical School, 1301 E Catherine, Ann Arbor, MI 48109 0606, USA
    Mol Microbiol 48:1017-28. 2003
    ..Our data are consistent with a hypothesis that AmtB interacts with PII and GlnK, and that co-transcription of glnK and amtB prevents titration of PII when AmtB is highly expressed...
  22. doi request reprint Load-induced modulation of signal transduction networks
    Peng Jiang
    Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI 48109 0606, USA
    Sci Signal 4:ra67. 2011
    ..Nodes in a signaling network are not independent relay devices, but rather are modulated by their downstream targets...
  23. ncbi request reprint Nac-mediated repression of the serA promoter of Escherichia coli
    Timothy A Blauwkamp
    Department of Biological Chemistry, University of Michigan Medical School, 1301 E Catherine, Ann Arbor, MI 48109 0606, USA
    Mol Microbiol 45:351-63. 2002
    ..We hypothesize that one role of Nac is to limit serine biosynthesis as part of a cellular mechanism to reduce metabolism in a co-ordinated manner when cells become starved for nitrogen...
  24. pmc Signaling properties of a covalent modification cycle are altered by a downstream target
    Alejandra C Ventura
    Department of Internal Medicine, Division of Hematology and Oncology and Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA
    Proc Natl Acad Sci U S A 107:10032-7. 2010
    ..Thus, we provide examples of how a downstream target can alter the signaling properties of an upstream signal transduction covalent modification cycle...
  25. ncbi request reprint Characterization of the GlnK protein of Escherichia coli
    M R Atkinson
    Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI 48109 0606, USA
    Mol Microbiol 32:301-13. 1999
    ....
  26. pmc Building biological memory by linking positive feedback loops
    Dong Eun Chang
    Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI 48109, USA
    Proc Natl Acad Sci U S A 107:175-80. 2010
    ..Our theoretical and experimental work shows how linked positive feedback loops may produce the robust bistable responses required in cellular networks that regulate development, the cell cycle, and many other cellular responses...
  27. ncbi request reprint Escherichia coli PII signal transduction protein controlling nitrogen assimilation acts as a sensor of adenylate energy charge in vitro
    Peng Jiang
    Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109 0606, USA
    Biochemistry 46:12979-96. 2007
    ..In the aggregate, our results show that PII proteins, in addition to serving as sensors of alpha-ketoglutarate, have the capacity to serve as direct sensors of the adenylylate energy charge...
  28. pmc Using two-component systems and other bacterial regulatory factors for the fabrication of synthetic genetic devices
    Alexander J Ninfa
    Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan, USA
    Methods Enzymol 422:488-512. 2007
    ....
  29. pmc The robustness of the Escherichia coli signal-transducing UTase/UR-PII covalent modification cycle to variation in the PII concentration requires very strong inhibition of the UTase activity of UTase/UR by glutamine
    Peng Jiang
    Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109 0606, United States
    Biochemistry 51:9032-44. 2012
    ....
  30. pmc Genetic and biochemical analysis of phosphatase activity of Escherichia coli NRII (NtrB) and its regulation by the PII signal transduction protein
    Augen A Pioszak
    Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109 0606, USA
    J Bacteriol 185:1299-315. 2003
    ..This suggests that the PII-binding site maps to the "back" of the C-terminal domain and that mutation of the ATP-lid, central domain, and N-terminal domain altered functions necessary for the phosphatase activity after PII binding...
  31. ncbi request reprint Structure-function analysis of glutamine synthetase adenylyltransferase (ATase, EC 2.7.7.49) of Escherichia coli
    Peng Jiang
    Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109 0606, USA
    Biochemistry 46:4117-32. 2007
    ..A model for the regulation of ATase by glutamine, PII, and PII-UMP consistent with all data is presented...
  32. ncbi request reprint Reconstitution of the signal-transduction bicyclic cascade responsible for the regulation of Ntr gene transcription in Escherichia coli
    P Jiang
    Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor 48109 0606, USA
    Biochemistry 37:12795-801. 1998
    ..Thus, the PII protein transduces the glutamine signal to the NRII-NRI monocycle in the form of its uridylylation state and is also the receptor of the antagonistic 2-ketoglutarate signal, which blocks the activity of unmodified PII...
  33. ncbi request reprint The regulation of Escherichia coli glutamine synthetase revisited: role of 2-ketoglutarate in the regulation of glutamine synthetase adenylylation state
    P Jiang
    Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor 48109 0606, USA
    Biochemistry 37:12802-10. 1998
    ..The possible biological implications of this regulatory arrangement are discussed...
  34. ncbi request reprint Response to comment on "'load-induced modulation of signal transduction networks': reconciling ultrasensitivity with bifunctionality?"
    Peng Jiang
    1Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI 48109 0606, USA
    Sci Signal 5:lc2. 2012
    ..Here, we argue that modeling the UTase/UR enzyme as a bifunctional enzyme with reciprocally regulated activity states misses important aspects of the system...
  35. ncbi request reprint Role of the GlnK signal transduction protein in the regulation of nitrogen assimilation in Escherichia coli
    M R Atkinson
    Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor 48109 0606, USA
    Mol Microbiol 29:431-47. 1998
    ..We hypothesize that one role of GlnK is to regulate the expression of the level of NRI-P during conditions of severe nitrogen starvation, and by so doing to contribute to the regulation of certain Ntr genes...
  36. pmc Structure/function analysis of the PII signal transduction protein of Escherichia coli: genetic separation of interactions with protein receptors
    P Jiang
    Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor 48109 0606, USA
    J Bacteriol 179:4342-53. 1997
    ..Thus, our results support the predictions made from structural studies that the exposed loops of PII and cleft formed at their interface are the sites of regulatory interactions...
  37. ncbi request reprint Reversible uridylylation of the Escherichia coli PII signal transduction protein regulates its ability to stimulate the dephosphorylation of the transcription factor nitrogen regulator I (NRI or NtrC)
    M R Atkinson
    Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor 48109 0606
    J Biol Chem 269:28288-93. 1994
    ..Thus, both the PII-UTase/UR and PII-NRII interactions display the continuous variability characteristic of rheostats as opposed to the binary variability characteristic of toggle switches...
  38. pmc Modular cell biology: retroactivity and insulation
    Domitilla Del Vecchio
    Department of Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, MI 48109, USA
    Mol Syst Biol 4:161. 2008
    ..We introduce, in particular, a mechanism based on a phosphorylation-dephosphorylation cycle. This mechanism enjoys a remarkable insulation property, due to the fast timescales of the phosphorylation and dephosphorylation reactions...
  39. pmc Rate constants rather than biochemical mechanism determine behaviour of genetic clocks
    Emery Conrad
    Mathematical Biology Research Group, Department of Mathematics, University of Michigan, Ann Arbor, MI 48109, USA
    J R Soc Interface 5:S9-15. 2008
    ..Here we show that either behaviour can be seen with either design and in a wide range of genetic clocks. This highlights the importance of parameters rather than biochemical mechanism in determining the system behaviour...
  40. ncbi request reprint Sensory components controlling bacterial nitrogen assimilation
    E S Kamberov
    Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor 48109 0606
    Cell Mol Biol Res 40:175-91. 1994
    ....
  41. ncbi request reprint The Escherichia coli PII signal transduction protein is activated upon binding 2-ketoglutarate and ATP
    E S Kamberov
    Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor 48109 0606, USA
    J Biol Chem 270:17797-807. 1995
    ..We hypothesize that nitrogen sensation in E. coli involves the separate measurement of glutamine by the UTase/UR protein and 2-ketoglutarate by the PII protein...
  42. doi request reprint Synthetic networks: oscillators and toggle switches for Escherichia coli
    Nicolas Perry
    Department of Biological Chemistry, Cellular Biotechnology Training Program, University of Michigan Medical School, Ann Arbor, MI, USA
    Methods Mol Biol 813:287-300. 2012
    ....
  43. ncbi request reprint Asymmetry in the autophosphorylation of the two-component regulatory system transmitter protein nitrogen regulator II of Escherichia coli
    P Jiang
    Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109 0606, USA
    Biochemistry 39:5057-65. 2000
    ..Experiments with heterodimers containing wild-type and mutant, nonphosphorylatable subunits suggested that the asymmetry of NRII autophosphorylation was not preexisting but resulted from the autophosphorylation of one subunit...
  44. pmc Probing interactions of the homotrimeric PII signal transduction protein with its receptors by use of PII heterotrimers formed in vitro from wild-type and mutant subunits
    P Jiang
    Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor 48109 0606, USA
    J Bacteriol 179:4354-60. 1997
    ..Thus, the G89A subunits, which contain an intact T-loop region, were not "repaired" by inclusion in heterotrimers along with delta47-53 subunits...
  45. ncbi request reprint Enzymological characterization of the signal-transducing uridylyltransferase/uridylyl-removing enzyme (EC 2.7.7.59) of Escherichia coli and its interaction with the PII protein
    P Jiang
    Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor 48109 0606, USA
    Biochemistry 37:12782-94. 1998
    ..Our kinetic data were consistent with the hypothesis that both transferase and uridylyl-removal reactions occurred at a single active center on the enzyme...
  46. ncbi request reprint Assay of prokaryotic enhancer activity over a distance in vitro
    Vladimir Bondarenko
    Department of Biochemistry and Molecular Biology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA
    Methods Enzymol 370:324-37. 2003

Research Grants20

  1. Development and Characterization of a Synthetic Clock
    Alexander Ninfa; Fiscal Year: 2004
    ....
  2. Structure/function analysis of the E. coli NIR/NRII signal transduction system
    Alexander Ninfa; Fiscal Year: 2007
    ..Our studies with a model system should allow rapid progress. ..
  3. Genetic Systems Bioengineering for Escherichia coli
    Alexander Ninfa; Fiscal Year: 2007
    ..In addition we propose designs for novel genetic clocks that test the role of various system design principles in the production of biological oscillations. ..
  4. Genetic Systems Bioengineering for Escherichia coli
    Alexander Ninfa; Fiscal Year: 2009
    ..In addition we propose designs for novel genetic clocks that test the role of various system design principles in the production of biological oscillations. ..
  5. Structure/Function Analysis of E. coli NRII
    Alexander Ninfa; Fiscal Year: 2004
    ..Together, these approaches should result in a mechanistic understanding of the NRII kinase and phosphatase activities and their regulation by PH and G1nK. ..
  6. INTERACTIONS OF THE SIGNAL TRANSDUCTION PROTEIN GLNK
    Alexander Ninfa; Fiscal Year: 2002
    ..These experiments should elucidate the design of the signal transduction system controlling nitrogen assimilation, and the mechanisms of interaction of PII and GlnK with their receptors and small molecule effectors. ..
  7. Structure/function analysis of the E. coli NIR/NRII signal transduction system
    Alexander Ninfa; Fiscal Year: 2009
    ..Our studies with a model system should allow rapid progress. ..