scholarly journals Going in GTP cycles in the nucleolus

2005 ◽  
Vol 168 (2) ◽  
pp. 177-178 ◽  
Author(s):  
Tom Misteli
Keyword(s):  
Signaling Pathways ◽  
Protein Targeting ◽  
Nucleolar Localization ◽  
Specific Localization ◽  
Extracellular Stimuli ◽  
Cellular Compartments ◽  
Increased Retention

Proteins are directed to cellular compartments by specific localization signals. A GTP-driven cycle has now been identified as a mechanism for protein targeting to the nucleolus. The involvement of a GTP switch suggests that nucleolar localization can be regulated and may be responsive to extracellular stimuli via signaling pathways. The uncovered mechanism also implies that localization is determined by increased retention rather than directed targeting.

scholarly journals The unpredictability of prolonged activation of stress response pathways

2015 ◽  
Vol 209 (6) ◽  
pp. 781-787 ◽  
Author(s):  
Lilian T. Lamech ◽  
Cole M. Haynes
Keyword(s):  
Stress Response ◽  
Signaling Pathways ◽  
Stress Responses ◽  
Degenerative Diseases ◽  
Response To Stress ◽  
Cellular Compartments

In response to stress, cellular compartments activate signaling pathways that mediate transcriptional programs to promote survival and reestablish homeostasis. Manipulation of the magnitude and duration of the activation of stress responses has been proposed as a strategy to prevent or repair the damage associated with aging or degenerative diseases. However, as these pathways likely evolved to respond specifically to transient perturbations, the unpredictability of prolonged activation should be considered.

scholarly journals Integrating Protein Localization with Automated Signaling Pathway Reconstruction

2019 ◽  
Author(s):  
Ibrahim Youssef ◽  
Jeffrey Law ◽  
Anna Ritz
Keyword(s):  
Signal Transduction ◽  
Signaling Pathways ◽  
Protein Interactions ◽  
Cellular Localization ◽  
Protein Localization ◽  
Dynamic Program ◽  
Reconstruction Algorithms ◽  
Ppi Networks ◽  
Cellular Compartments ◽  
Localization Information

AbstractUnderstanding cellular responses via signal transduction is a core focus in systems biology. Tools to automatically reconstruct signaling pathways from protein-protein interactions (PPIs) can help biologists generate testable hypotheses about signaling. However, automatic reconstruction of signaling pathways suffers from many interactions with the same confidence score leading to many equally good candidates. Further, some reconstructions are biologically misleading due to ignoring protein localization information. We proposeLocPL, a method to improve the automatic reconstruction of signaling pathways from PPIs by incorporating information about protein localization in the reconstructions. The method relies on a dynamic program to ensure that the proteins in a reconstruction are localized in cellular compartments that are consistent with signal transduction from the membrane to the nucleus.LocPLand existing reconstruction algorithms are applied to two PPI networks and assessed using both global and local definitions of accuracy.LocPLproduces more accurate and biologically meaningful reconstructions on a versatile set of signaling pathways.LocPLis a powerful tool to automatically reconstruct signaling pathways from PPIs that leverages cellular localization information about proteins. The underlying dynamic program and signaling model are flexible enough to study cellular signaling under different settings of signaling flow across the cellular compartments.

scholarly journals Identification of Protein Complexes Associated with the Usher Syndrome 2C and Epilepsy-Associated Protein VLGR1 Applying Affinity Proteomics

2017 ◽  
Vol 4 (1) ◽  
pp. 100051 ◽  
Author(s):  
Barbara Knapp ◽  
Deva Krupakar Kusuluri ◽  
Nicola Horn ◽  
Karsten Boldt ◽  
Marius Ueffing ◽  
...  
Keyword(s):  
High Resolution ◽  
Signaling Pathways ◽  
Protein Complexes ◽  
Usher Syndrome ◽  
Protein Networks ◽  
Cellular Compartments ◽  
Affinity Proteomics ◽  
Shed Light

Authors aimed to identify novel VLGR1-associated protein networks to shed light on its integration into signaling pathways and the cellular compartments in which VLGR1 functions using high-resolution affinity proteomics based on tandem affinity purifications (TAPs).

scholarly journals Physiopathological Implications of 7TM Receptors

2010 ◽  
Vol 6 ◽  
pp. 33-47
Author(s):  
Adam I. Cygankiewicz
Keyword(s):  
Retinitis Pigmentosa ◽  
Signaling Pathways ◽  
Intracellular Signaling ◽  
Severe Obesity ◽  
Aberrant Expression ◽  
Intracellular Signaling Pathways ◽  
Extracellular Stimuli ◽  
7Tm Receptors

Seven-transmembrane (7TM) receptors are one of the most important proteins involved in perception of extracellular stimuli and regulation of variety of intracellular signaling pathways. Divergence of receptor types, their ligands and signaling pathways makes 7TM receptors important factors in pathology of many diseases. This review focused on the main diseases in which involvement of 7TM receptors was established e.g., retinitis pigmentosa, severe obesity, and dwarfism. Recent findings of aberrant expression of 7TM receptors in development of cancer were also summarized.

scholarly journals Subcellular Golgi localization of stathmin family proteins is promoted by a specific set of DHHC palmitoyl transferases

2011 ◽  
Vol 22 (11) ◽  
pp. 1930-1942 ◽  
Author(s):  
Aurore D. Levy ◽  
Véronique Devignot ◽  
Yuko Fukata ◽  
Masaki Fukata ◽  
André Sobel ◽  
...  
Keyword(s):  
Brefeldin A ◽  
Membrane Association ◽  
Lipid Modification ◽  
Subcellular Membrane ◽  
Local Functions ◽  
Peripheral Proteins ◽  
Protein Palmitoylation ◽  
Extracellular Stimuli ◽  
Cellular Compartments ◽  
Membrane Anchoring

 Protein palmitoylation is a reversible lipid modification that plays critical roles in protein sorting and targeting to specific cellular compartments. The neuronal microtubule-regulatory phosphoproteins of the stathmin family (SCG10/stathmin 2, SCLIP/stathmin 3, and RB3/stathmin 4) are peripheral proteins that fulfill specific and complementary roles in the formation and maturation of the nervous system. All neuronal stathmins are localized at the Golgi complex and at vesicles along axons and dendrites. Their membrane anchoring results from palmitoylation of two close cysteine residues present within their homologous N-terminal targeting domains. By preventing palmitoylation with 2-bromopalmitate or disrupting the integrity of the Golgi with brefeldin A, we were able to show that palmitoylation of stathmins 2 and 3 likely occurs at the Golgi and is crucial for their specific subcellular localization and trafficking. In addition, this membrane binding is promoted by a specific set of palmitoyl transferases that localize with stathmins 2 and 3 at the Golgi, directly interact with them, and enhance their membrane association. The subcellular membrane–associated microtubule-regulatory activity of stathmins might then be fine-tuned by extracellular stimuli controlling their reversible palmitoylation, which can be viewed as a crucial regulatory process for specific and local functions of stathmins in neurons.

scholarly journals Insights into Nuclear G-Protein-Coupled Receptors as Therapeutic Targets in Non-Communicable Diseases

2021 ◽  
Vol 14 (5) ◽  
pp. 439
Author(s):  
Salomé Gonçalves-Monteiro ◽  
Rita Ribeiro-Oliveira ◽  
Maria Sofia Vieira-Rocha ◽  
Martin Vojtek ◽  
Joana B. Sousa ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
G Protein ◽  
Communicable Disease ◽  
G Protein Coupled Receptors ◽  
Metabotropic Glutamate ◽  
Secretin Receptor ◽  
Class B ◽  
Fungal Mating ◽  
Extracellular Stimuli ◽  
G Protein Coupled

G-protein-coupled receptors (GPCRs) comprise a large protein superfamily divided into six classes, rhodopsin-like (A), secretin receptor family (B), metabotropic glutamate (C), fungal mating pheromone receptors (D), cyclic AMP receptors (E) and frizzled (F). Until recently, GPCRs signaling was thought to emanate exclusively from the plasma membrane as a response to extracellular stimuli but several studies have challenged this view demonstrating that GPCRs can be present in intracellular localizations, including in the nuclei. A renewed interest in GPCR receptors’ superfamily emerged and intensive research occurred over recent decades, particularly regarding class A GPCRs, but some class B and C have also been explored. Nuclear GPCRs proved to be functional and capable of triggering identical and/or distinct signaling pathways associated with their counterparts on the cell surface bringing new insights into the relevance of nuclear GPCRs and highlighting the nucleus as an autonomous signaling organelle (triggered by GPCRs). Nuclear GPCRs are involved in physiological (namely cell proliferation, transcription, angiogenesis and survival) and disease processes (cancer, cardiovascular diseases, etc.). In this review we summarize emerging evidence on nuclear GPCRs expression/function (with some nuclear GPCRs evidencing atypical/disruptive signaling pathways) in non-communicable disease, thus, bringing nuclear GPCRs as targets to the forefront of debate.

scholarly journals Branching and Mixing: New Signals of the Ubiquitin Signaling System

2020 ◽  
Author(s):  
Daniel Perez-Hernandez ◽  
Marta L. Mendes ◽  
Gunnar Dittmar
Keyword(s):  
Protein Degradation ◽  
Posttranslational Modifications ◽  
Protein Targeting ◽  
Ubiquitin Chain ◽  
Multiple Signals ◽  
Additional Layer ◽  
Ubiquitin System ◽  
Ubiquitin Molecule ◽  
A Chain ◽  
Cellular Compartments

Posttranslational modifications allow cells and organisms to adapt to their environment without the need to synthesize new proteins. The ubiquitin system is one of the most versatile modification systems as it does not only allow a simple on–off modification but, by forming a chain of ubiquitin molecules, allows conveying multiple signals. The structure of the chains is dependent on the linkage to the previous ubiquitin molecule as every lysine can serve as an acceptor point for this modification. Different chain types code for specific signals ranging from protein degradation to protein targeting different cellular compartments. Recently the code of ubiquitin signals has been further expanded as branching and mixing of different chain types has been detected. As an additional layer of complexity, modifications of the ubiquitin chain by ubiquitin-like modifiers, like NEDD8, SUMO, or ISG15, have been found. Here we will discuss the different chain types and the technical challenges which are associated with analyzing ubiquitin topology-based signaling.

scholarly journals The RAS GTPase RIT1 compromises mitotic fidelity through spindle assembly checkpoint suppression

2020 ◽  
Author(s):  
Antonio Cuevas-Navarro ◽  
Richard Van ◽  
Alice Cheng ◽  
Anatoly Urisman ◽  
Pau Castel ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Chromosome Segregation ◽  
Spindle Assembly Checkpoint ◽  
Spindle Assembly ◽  
Mitotic Checkpoint ◽  
Ras Gtpases ◽  
Safety Mechanism ◽  
Evolutionarily Conserved ◽  
Ras Family ◽  
Extracellular Stimuli

SUMMARYThe spindle assembly checkpoint (SAC) is an evolutionarily conserved safety mechanism that maintains genomic stability. However, despite the understanding of the fundamental mechanisms that control the SAC, it remains unknown how signaling pathways directly interact with and regulate the mitotic checkpoint activity. In response to extracellular stimuli, a diverse network of signaling pathways involved in cell growth, survival, and differentiation are activated and this process is prominently regulated by the Ras family of GTPases. Here we show that RIT1, a Ras-related GTPase, is essential for timely progression through mitosis and proper chromosome segregation. Furthermore, pathogenic levels of RIT1 silence the SAC, accelerate transit through mitosis, and promote chromosome segregation errors through direct association with SAC proteins MAD2 and p31comet. Our results highlight a unique function of RIT1 compared to other Ras GTPases and elucidate a direct link between a signaling pathway and the SAC through a novel regulatory mechanism.Graphical Abstract

scholarly journals ERK and β-Arrestin Interaction

2014 ◽  
Vol 20 (3) ◽  
pp. 341-349 ◽  
Author(s):  
Haifeng Eishingdrelo ◽  
Wei Sun ◽  
Hua Li ◽  
Li Wang ◽  
Alex Eishingdrelo ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Protein Interactions ◽  
Tyrosine Kinases ◽  
Intracellular Signaling ◽  
Kinase Inhibitors ◽  
Adaptor Protein ◽  
Direct Interaction ◽  
Signal Pathways ◽  
Surface Receptors ◽  
Extracellular Stimuli

β-Arrestin, a signal adaptor protein, mediates intracellular signal transductions through protein-protein interactions by bringing two or more proteins in proximity. Extracellular signal-regulated kinase (ERK), a protein kinase in the family of mitogen-activated protein kinases (MAPKs), is involved in various receptor signal pathways. Interaction of ERK with β-arrestin or formation of ERK/β-arrestin signal complex occurs in response to activation of a variety of cell surface receptors. The ERK/β-arrestin signal complex may be a common transducer to converge a variety of extracellular stimuli to similar downstream intracellular signaling pathways. By using a cell-based protein-protein interaction LinkLight assay technology, we demonstrate a direct interaction between ERK and β-arrestin in response to extracellular stimuli, which can be sensitively and quantitatively monitored. Activations of G protein–coupled receptors (GPCRs), receptor tyrosine kinases (RTKs), and cytokine receptors promote formation of the ERK/β-arrestin signal complex. Our data indicate that the ERK/β-arrestin signal complex is a common transducer that participates in a variety of receptor signaling pathways. Furthermore, we demonstrate that receptor antagonists or kinase inhibitors can block the agonist-induced ERK and β-arrestin interaction. Thus, the ERK/β-arrestin interaction assay is useful for screening of new receptor modulators.

scholarly journals Phosphorylation of SNX27 by MAPK11/14 links cellular stress–signaling pathways with endocytic recycling

2021 ◽  
Vol 220 (4) ◽  
Author(s):  
Lejiao Mao ◽  
Chenyi Liao ◽  
Jiao Qin ◽  
Yanqiu Gong ◽  
Yifei Zhou ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Cellular Stress ◽  
Binding Pocket ◽  
Stress Signaling ◽  
Lysosomal Degradation ◽  
Endocytic Recycling ◽  
Cargo Proteins ◽  
Extracellular Stimuli ◽  
Save Energy ◽  
Golgi Network

Endocytosed proteins can be delivered to lysosomes for degradation or recycled to either the trans-Golgi network or the plasma membrane. It remains poorly understood how the recycling versus degradation of cargoes is determined. Here, we show that multiple extracellular stimuli, including starvation, LPS, IL-6, and EGF treatment, can strongly inhibit endocytic recycling of multiple cargoes through the activation of MAPK11/14. The stress-induced kinases in turn directly phosphorylate SNX27, a key regulator of endocytic recycling, at serine 51 (Ser51). Phosphorylation of SNX27 at Ser51 alters the conformation of its cargo-binding pocket and decreases the interaction between SNX27 and cargo proteins, thereby inhibiting endocytic recycling. Our study indicates that endocytic recycling is highly dynamic and can crosstalk with cellular stress–signaling pathways. Suppression of endocytic recycling and enhancement of receptor lysosomal degradation serve as new mechanisms for cells to cope with stress and save energy.

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