Response to comment on "'load-induced modulation of signal transduction networks': reconciling ultrasensitivity with bifunctionality?".

1Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI 48109-0606, USA.
Science Signaling (Impact Factor: 6.28). 01/2012; 5(205):lc2. DOI: 10.1126/scisignal.2002716
Source: PubMed


Straube suggests that a model that reflects the bifunctional nature of the cycle enzyme uridylyltransferase/uridylyl-removing enzyme (UTase/UR) should be used, in which the UT and UR activities are distinct and reciprocally regulated activity states of the enzyme, and notes that if such a model is used, the effects of retroactivity at intermediate stimulation will be different. However, such a model does not accurately match the observed enzyme regulatory properties and fails to predict the ultrasensitive response obtained in the experiments. Here, we argue that modeling the UTase/UR enzyme as a bifunctional enzyme with reciprocally regulated activity states misses important aspects of the system.

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    ABSTRACT: SUMMARY We present a comprehensive overview of the hierarchical network of intracellular processes revolving around central nitrogen metabolism in Escherichia coli. The hierarchy intertwines transport, metabolism, signaling leading to posttranslational modification, and transcription. The protein components of the network include an ammonium transporter (AmtB), a glutamine transporter (GlnHPQ), two ammonium assimilation pathways (glutamine synthetase [GS]-glutamate synthase [glutamine 2-oxoglutarate amidotransferase {GOGAT}] and glutamate dehydrogenase [GDH]), the two bifunctional enzymes adenylyl transferase/adenylyl-removing enzyme (ATase) and uridylyl transferase/uridylyl-removing enzyme (UTase), the two trimeric signal transduction proteins (GlnB and GlnK), the two-component regulatory system composed of the histidine protein kinase nitrogen regulator II (NRII) and the response nitrogen regulator I (NRI), three global transcriptional regulators called nitrogen assimilation control (Nac) protein, leucine-responsive regulatory protein (Lrp), and cyclic AMP (cAMP) receptor protein (Crp), the glutaminases, and the nitrogen-phosphotransferase system. First, the structural and molecular knowledge on these proteins is reviewed. Thereafter, the activities of the components as they engage together in transport, metabolism, signal transduction, and transcription and their regulation are discussed. Next, old and new molecular data and physiological data are put into a common perspective on integral cellular functioning, especially with the aim of resolving counterintuitive or paradoxical processes featured in nitrogen assimilation. Finally, we articulate what still remains to be discovered and what general lessons can be learned from the vast amounts of data that are available now.
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