The role of effector molecules in signal transduction by PII proteins

2011 ◽  
Vol 39 (1) ◽  
pp. 189-194 ◽  
Author(s):  
Martha Radchenko ◽  
Mike Merrick
Keyword(s):  
Signal Transduction ◽  
Great Majority ◽  
Complex Structures ◽  
Effector Molecules ◽  
Protein Protein Interaction ◽  
Wide Range ◽  
Pii Proteins ◽  
Regulatory Effects ◽  
Signal Transduction Proteins

PII proteins are one of the most widely distributed signal transduction proteins in Nature, being ubiquitous in bacteria, archaea and plants. They act by protein–protein interaction to control the activities of a wide range of enzymes, transcription factors and transport proteins, the great majority of which are involved in cellular nitrogen metabolism. The regulatory activities of PII proteins are mediated through their ability to bind the key effector metabolites 2-OG (2-oxoglutarate), ATP and ADP. However, the molecular basis of these regulatory effects remains unclear. Recent advances in the solution of the crystal structures of PII proteins complexed with some of their target proteins, as well as the identification of the ATP/ADP- and 2-OG-binding sites, have improved our understanding of their mode of action. In all of the complex structures solved to date, the flexible T-loops of PII facilitate interaction with the target protein. The effector molecules appear to play a key role in modulating the conformation of the T-loops and thereby regulating the interactions between PII and its targets.

scholarly journals The Role of Cgrp-Receptor Component Protein (Rcp) in Cgrp-Mediated Signal Transduction

2001 ◽  
Vol 1 ◽  
pp. 12-12
Author(s):  
M. A. Prado ◽  
B. Evans-Bain ◽  
S. L. Santi ◽  
I. M. Dickerson
Keyword(s):  
Signal Transduction ◽  
Cgrp Receptor ◽  
Nih3t3 Cells ◽  
New Class ◽  
Receptor Component ◽  
Calcitonin Gene ◽  
Cellular Signal ◽  
Signal Transduction Proteins ◽  
Component Protein

The calcitonin gene-related peptide (CGRP)-receptor component protein (RCP) is a 17-kDa intracellular peripheral membrane protein required for signal transduction at CGRP receptors. To determine the role of RCP in CGRP-mediated signal transduction, RCP was depleted from NIH3T3 cells using antisense strategy. Loss of RCP protein correlated with loss of cAMP production by CGRP in the antisense cells. In contrast, loss of RCP had no effect on CGRP-mediated binding; therefore RCP is not acting as a chaperone for the CGRP receptor. Instead, RCP is a novel signal transduction molecule that couples the CGRP receptor to the cellular signal transduction machinery. RCP thus represents a prototype for a new class of signal transduction proteins that are required for regulation of G protein-coupled receptors.

scholarly journals Context-Dependent Functions of the PII and GlnK Signal Transduction Proteins in Escherichia coli

2002 ◽  
Vol 184 (19) ◽  
pp. 5364-5375 ◽  
Author(s):  
Mariette R. Atkinson ◽  
Timothy A. Blauwkamp ◽  
Alexander J. Ninfa
Keyword(s):  
Escherichia Coli ◽  
Signal Transduction ◽  
Environmental Conditions ◽  
Nitrogen Assimilation ◽  
Cellular Level ◽  
Unknown Mechanism ◽  
Wide Range ◽  
Fine Control ◽  
Context Dependent ◽  
Signal Transduction Proteins

ABSTRACT Two closely related signal transduction proteins, PII and GlnK, have distinct physiological roles in the regulation of nitrogen assimilation. Here, we examined the physiological roles of PII and GlnK when these proteins were expressed from various regulated or constitutive promoters. The results indicate that the distinct functions of PII and GlnK were correlated with the timing of expression and levels of accumulation of the two proteins. GlnK was functionally converted into PII when its expression was rendered constitutive and at the appropriate level, while PII was functionally converted into GlnK by engineering its expression from the nitrogen-regulated glnK promoter. Also, the physiological roles of both proteins were altered by engineering their expression from the nitrogen-regulated glnA promoter. We hypothesize that the use of two functionally identical PII-like proteins, which have distinct patterns of expression, may allow fine control of Ntr genes over a wide range of environmental conditions. In addition, we describe results suggesting that an additional, unknown mechanism may control the cellular level of GlnK.

scholarly journals The cyclic di-GMP network is a global regulator of phase-transition and attachment-dependent host colonization in Erwinia amylovora

2021 ◽  
Author(s):  
Roshni R. Kharadi ◽  
Kayla Selbmann ◽  
George W. Sundin
Keyword(s):  
Signal Transduction ◽  
Biofilm Formation ◽  
Erwinia Amylovora ◽  
Initial Surface ◽  
Diguanylate Cyclase ◽  
Wide Range ◽  
Biofilm Development ◽  
Bacterial Systems

AbstractCyclic-di-GMP (c-di-GMP) is an essential bacterial second messenger that regulates the transition to biofilm formation in the phytopathogen Erwinia amylovora. The c-di-GMP system in E. amylovora is comprised of 12 diguanylate cyclase/Edc (dimerize cyclic-di-GMP) and phosphodiesterase/Pde (hydrolyze cyclic-di-GMP) proteins that are characterized by the presence of GGDEF and/or EAL motifs in their domain architecture. In order to study the global regulatory effect (without the inclusion of systemic regulatory impedance) of the c-di-GMP system in E. amylovora, we eliminated all 12 edc and pde genes in E. amylovora Ea1189Δ12. Comparisons between the representative transcriptomic profiles of Ea1189Δ12 and the combinatorial edc gene knockout mutant (Ea1189Δ5) revealed marked overall distinctions in expression levels for targets in a wide range of regulatory categories, including metabolic pathways involved in the utilization of methionine, isoleucine, histidine, etc. as well as critical signal transduction pathways including the Rcs phosphorelay and PhoPQ system. A complete loss of the cyclic-di-GMP signaling components resulted in the inability of Ea1189Δ12 cells to attach to and form biofilms in vitro and within the xylem vasculature in apple shoots. Using a flow-based in vitro biofilm system, we found that initial surface sensing was primarily dependent on the flagellar filament (FliC), following which the type IV pilus (HofC) was required to anchor cells to the surface to initialize biofilm development. A transcriptomic analysis of WT E. amylovora Ea1189 and Ea1189Δ12 cells in various stages of biofilm development revealed that cyclic-di-GMP based regulation had widespread effects on purine and pyrimidine biosynthesis pathways, amylovoran biosynthesis genes and the EnvZ/OmpR signal transduction system. Additionally, complementing individual eliminated genes back into Ea1189Δ12, and the collective evaluation of several virulence factors, enabled the correlative clustering of the functional effect rendered by each Edc and Pde enzyme in the system.SignificanceCyclic-di-GMP dependent regulation, in the context of biofilm formation, has been studied in several bacterial systems. However, the comprehensiveness of the studies exploring the role of individual genetic components related to cyclic-di-GMP is affected by the often large number of diguanylate cyclase and phosphodiesterase enzymes present within individual bacterial systems. To explore the evolutionary dependencies related to cyclic-di-GMP in E. amylovora, we used a collective elimination approach, whereby all of the enzymes involved in cyclic-di-GMP metabolism were eliminated from the system. This approach enabled us to highlight the critical importance of cyclic-di-GMP in plant xylem colonization due to its effect on surface attachment. Additionally, we highlight the global transcriptomic effect of cyclic-di-GMP dependent signaling at various stages of biofilm development. Our approach is aimed at exploring the regulatory role of individual cyclic-di-GMP related enzymes in a background that is free from any redundancy-based feedback.

scholarly journals The PopN gate-keeper complex acts on the ATPase PscN to regulate the T3SS secretion switch from early to middle substrates in Pseudomonas aeruginosa

2020 ◽  
Author(s):  
Tuan-Dung Ngo ◽  
Caroline Perdu ◽  
Bakhos Jneid ◽  
Michel Ragno ◽  
Julia Novion Ducassou ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Type Iii Secretion ◽  
Secreted Proteins ◽  
List Type ◽  
Protein Protein Interaction ◽  
Microscale Thermophoresis ◽  
Wide Range ◽  
Chaperone Complex ◽  
Bacterial Cytoplasm

AbstractPseudomonas aeruginosa is an opportunistic bacterium of which the main virulence factor is the Type III Secretion System. The ATPase of this machinery, PscN (SctN), is thought to be localized at the base of the secretion apparatus and to participate in the recognition, chaperone dissociation and unfolding of exported T3SS proteins. In this work, a protein-protein interaction ELISA revealed the interaction of PscN with a wide range of exported T3SS proteins including the needle, translocator, gate-keeper and effector. These interactions were further confirmed by Microscale Thermophoresis that also indicated a preferential interaction of PscN with secreted proteins or protein-chaperone complex rather than with chaperones alone, in line with the release of the chaperones in the bacterial cytoplasm after the dissociation from their exported proteins. Moreover, we suggest a new role of the gate-keeper complex and the ATPase in the regulation of early substrates recognition by the T3SS. This finding sheds a new light on the mechanism of secretion switching from early to middle substrates in P. aeruginosa.HighlightsT3SS substrates are secreted sequentially but information on the switches are missingInteraction of the T3SS ATPase with secreted proteins were investigated by different approachesMicroscale Thermophoresis revealed a lower affinity for chaperones alone compared to complexesThe Gate-keeper complex binds to the ATPase and increases its affinity for the needle complexA new role of the Gate-keeper complex is proposed, directly acting on the T3SS ATPase

scholarly journals Contribution of Janus-Kinase/Signal Transduction Activator of Transcription Pathway in the Pathogenesis of Vasculitis: A Possible Treatment Target in the Upcoming Future

2021 ◽  
Vol 12 ◽  
Author(s):  
Roberto Bursi ◽  
Giacomo Cafaro ◽  
Carlo Perricone ◽  
Ilenia Riccucci ◽  
Santina Calvacchi ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Real Life ◽  
Signal Transduction Pathway ◽  
Janus Kinase ◽  
Jak Inhibitors ◽  
Treatment Target ◽  
Real Life Data ◽  
Wide Range

Janus-kinase (JAK) and signal transduction activator of transcription (STAT) signal transduction pathway is involved in a wide range of physiological and pathological processes, including in the pathogenesis of several autoimmune diseases. Data supporting the role of JAK/STAT in the development of vasculitis are limited and mostly focused on large vessel vasculitis and Behçet’s disease. In this review, we provide a thorough picture of currently available evidence on the topic, gathered from in vitro experiments, animal models and human real-life data, analyzing the rationale for the use of JAK inhibitors for the management of vasculitis. Overall, despite a very strong biological and pathogenic basis, data are too few to recommend this therapeutic approach, beyond very severe and refractory forms of vasculitis. However, for the same reasons, a strong scientific effort in this direction is indeed worthwhile.

Working toward a synthesis

2016 ◽  
Vol 27 (4) ◽  
pp. 465-477 ◽  
Author(s):  
Ronald W. Langacker
Keyword(s):  
Quantitative Methods ◽  
Cognitive Linguistics ◽  
Cognitive Grammar ◽  
Complex Structures ◽  
The Social ◽  
Wide Range ◽  
Processing Activity ◽  
Linguistic Units ◽  
Made In

AbstractAlthough Cognitive Linguistics represents a recontextualization with respect to prior tradition, internally it has been diverse and grounded from the outset. In design and principle, this holds for Cognitive Grammar, which seeks a comprehensive yet unified account of structure and use. It foreshadowed the “social turn” by claiming that the speaker-hearer interaction is inherent in linguistic units, which are abstracted from usage events; and also the “quantitative turn”, by its usage-based nature and the view that structure resides in processing activity. There is no single way of describing a language, just as there is no single way of describing a biological organism. Linguistics is thus a vast, multifaceted enterprise embracing a wide range of objectives, methods, and expertise. A number of points are made in this regard. (i) While corpus analysis is essential for many purposes, elicited and introspective data also have their place. (ii) With no inconsistency, language is validly characterized as both a cognitive/mental phenomenon and a social/interactive one. (iii) The fact that language resides in processing activity does not entail the absence of discreteness or the non-existence of complex structures. (iv) The importance of quantitative methods does not obviate the central role of structural analysis and description, which have equal claim to being empirical.

Dietary zinc deficiency and expression of T lymphocyte signal transduction proteins

2000 ◽  
Vol 78 (10) ◽  
pp. 823-828 ◽  
Author(s):  
Carla G Taylor ◽  
Jeri-Anne C Giesbrecht
Keyword(s):  
Signal Transduction ◽  
T Lymphocytes ◽  
Immune Function ◽  
T Lymphocyte ◽  
Molecular Level ◽  
Immune Dysfunction ◽  
Zn Deficiency ◽  
Dietary Zinc ◽  
Signal Transduction Proteins

Impaired immune function in dietary zinc (Zn) deficiency is characterized in part by reduced lymphocyte numbers (lymphopenia) and depressed cell-mediated (T lymphocyte) immune function, however, the causative mechanisms at the molecular level have not been elucidated. This paper will focus on the role of dietary Zn in T lymphocyte signal transduction, and specifically, the early Zn-dependent steps for phosphorylation and the putative Zn-finger proteins or Zn-metalloenzymes that may be part of the molecular mechanism for explaining immune dysfunction in Zn deficiency. One of the major recent findings is that murine splenic T lymphocyte p56lck expression is elevated in dietary Zn deficiency and caloric deficiency. Based on the known functions of p56lck, it is proposed that elevated p56lck may contribute to altered thymocyte maturation, apoptosis, and lymphopenia in dietary Zn deficiency and other malnutrition syndromes.Key words: zinc, T lymphocytes, signal transduction, immune function.

scholarly journals The Potential Role of REG Family Proteins in Inflammatory and Inflammation-Associated Diseases of the Gastrointestinal Tract

2021 ◽  
Vol 22 (13) ◽  
pp. 7196
Author(s):  
Chao Sun ◽  
Xiaoyu Wang ◽  
Yangyang Hui ◽  
Hirokazu Fukui ◽  
Bangmao Wang ◽  
...  
Keyword(s):  
Potential Role ◽  
Structural Features ◽  
The Body ◽  
Current Evidence ◽  
Gi Tract ◽  
Associated Diseases ◽  
Wide Range ◽  
Colitic Cancer ◽  
Regulatory Effects

Regenerating gene (REG) family proteins serve as multifunctional secretory molecules with trophic, antiapoptotic, anti-inflammatory, antimicrobial and probably immuno-regulatory effects. Since their discovery, accumulating evidence has clarified the potential roles of the REG family in the occurrence, progression and development of a wide range of inflammatory and inflammation-associated diseases of the gastrointestinal (GI) tract. However, significant gaps still exist due to the undefined nature of certain receptors, regulatory signaling pathways and possible interactions among distinct Reg members. In this narrative review, we first describe the structural features, distribution pattern and purported regulatory mechanisms of REG family proteins. Furthermore, we summarize the established and proposed roles of REG proteins in the pathogenesis of various inflammation-associated pathologies of the GI tract and the body as a whole, focusing particularly on carcinogenesis in the ulcerative colitis—colitic cancer sequence and gastric cancer. Finally, the clinical relevance of REG products in the context of diagnosis, treatment and prognostication are also discussed in detail. The current evidence suggests a need to better understanding the versatile roles of Reg family proteins in the pathogenesis of inflammatory-associated diseases, and their broadened future usage as therapeutic targets and prognostic biomarkers is anticipated.

POPDC proteins and cardiac function

2019 ◽  
Vol 47 (5) ◽  
pp. 1393-1404 ◽  
Author(s):  
Thomas Brand
Keyword(s):  
Potential Role ◽  
Striated Muscle ◽  
Short Review ◽  
Effector Proteins ◽  
Muscle Disease ◽  
Disease Genes ◽  
Protein Protein Interaction ◽  
Interaction Partners ◽  
And Function

Abstract The Popeye domain-containing gene family encodes a novel class of cAMP effector proteins in striated muscle tissue. In this short review, we first introduce the protein family and discuss their structure and function with an emphasis on their role in cyclic AMP signalling. Another focus of this review is the recently discovered role of POPDC genes as striated muscle disease genes, which have been associated with cardiac arrhythmia and muscular dystrophy. The pathological phenotypes observed in patients will be compared with phenotypes present in null and knockin mutations in zebrafish and mouse. A number of protein–protein interaction partners have been discovered and the potential role of POPDC proteins to control the subcellular localization and function of these interacting proteins will be discussed. Finally, we outline several areas, where research is urgently needed.

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