scholarly journals Phosphorylation and Dephosphorylation of Tau Protein by the Catalytic Subunit of PKA, as Probed by Electrophoretic Mobility Retard

2020 ◽  
pp. 1-14
Author(s):  
María J. Benítez ◽  
Raquel Cuadros ◽  
Juan S. Jiménez
Keyword(s):  
Protein Kinases ◽  
Electrophoretic Mobility ◽  
Energy State ◽  
Paired Helical Filaments ◽  
Catalytic Subunit ◽  
Relative Electrophoretic Mobility ◽  
Mitochondrial Functions ◽  
Phosphorylation Reaction ◽  
The Stability ◽  
Hyperphosphorylated Form

Background: Tau is a microtubule associated protein that regulates the stability of microtubules and the microtubule-dependent axonal transport. Its hyperphosphorylated form is one of the hallmarks of Alzheimer’s disease and other tauopathies and the major component of the paired helical filaments that form the abnormal proteinaceous tangles found in these neurodegenerative diseases. It is generally accepted that the phosphorylation extent of tau is the result of an equilibrium in the activity of protein kinases and phosphatases. Disruption of the balance between both types of enzyme activities has been assumed to be at the origin of tau hyperphosphorylation and the subsequent toxicity and progress of the disease. Objective: We explore the possibility that, beside the phosphatase action on phosphorylated tau, the catalytic subunit of PKA catalyzes both tau phosphorylation and also tau dephosphorylation, depending on the ATP/ADP ratio. Methods: We use the shift in the relative electrophoretic mobility suffered by different phosphorylated forms of tau, as a sensor of the catalytic action of the enzyme. Results: The results are in agreement with the long-known thermodynamic reversibility of the phosphorylation reaction (ATP + Protein = ADP+Phospho-Protein) catalyzed by PKA and many other protein kinases. Conclusion: The results contribute to put the compartmentalized energy state of the neuron and the mitochondrial-functions disruption upstream of tau-related pathologies.

cAMP-dependent protein kinases in the rat testis: regulatory and catalytic subunit associations

1992 ◽  
Vol 1136 (2) ◽  
pp. 208-218 ◽  
Author(s):  
Jeffrey Weiss ◽  
Deborah A. DeManno ◽  
Richard E. Cutler ◽  
Edward J. Brooks ◽  
Jack Erlichman ◽  
...  
Keyword(s):  
Protein Kinases ◽  
Catalytic Subunit ◽  
Rat Testis ◽  
Dependent Protein

Simple Leg Placement Strategy for a One Legged Running Model

2012 ◽  
Author(s):  
Timothy Sullivan ◽  
Justin Seipel
Keyword(s):  
Stance Phase ◽  
Energy State ◽  
Center Of Mass ◽  
Mass Movement ◽  
Legged Locomotion ◽  
Energy Conserving ◽  
Lower Torque ◽  
The Stability ◽  
Time Required ◽  
Torque Values

The Spring Loaded Inverted Pendulum (SLIP) model was developed to describe center of mass movement patterns observed in animals, using only a springy leg and a point mass. However, SLIP is energy conserving and does not accurately represent any biological or robotic system. Still, this model is often used as a foundation for the investigation of improved legged locomotion models. One such model called Torque Damped SLIP (TD-SLIP) utilizes two additional parameters, a time dependent torque and dampening to drastically increase the stability. Forced Damped SLIP (FD-SLIP), a predecessor of TD-SLIP, has shown that this model can be further simplified by using a constant torque, instead of a time varying torque, while still maintaining stability. Using FD-SLIP as a base, this paper explores a leg placement strategy using a simple PI controller. The controller takes advantage of the fact that the energy state of FD-SLIP is symmetric entering and leaving the stance phase during steady state conditions. During the flight phase, the touch down leg angle is adjusted so that the energy dissipation due to dampening, during the stance phase, compensates for any imbalance of energy. This controller approximately doubles the region of stability when subjected to velocity perturbations at touchdown, enables the model to operate at considerably lower torque values, and drastically reduces the time required to recover from a perturbation, while using less energy. Finally, the leg placement strategy used effectively imitates the natural human response to velocity perturbations while running.

scholarly journals Communication: On the Stability and Necessary Electrophoretic Mobility of Bare Oil Nanodroplets in Water

2020 ◽  
Author(s):  
Saranya Pullanchery ◽  
Sergey Kulik ◽  
halil okur ◽  
Hilton. B. de Aguiar ◽  
Sylvie Roke
Keyword(s):  
Electrophoretic Mobility ◽  
Dlvo Theory ◽  
Air Bubbles ◽  
Oil Droplets ◽  
Cleaning Procedure ◽  
Charged Droplets ◽  
Oil In Water ◽  
The Creation ◽  
The Stability ◽  
The 19Th Century

Hydrophobic oil droplets, particles and air bubbles can be dispersed in water as kinetically stabilized dispersions. It has been established since the 19th century that such objects harbor a negative electrostatic potential roughly twice larger than the thermal energy. The source of this charge continues to be one of the core observations in relation to hydrophobicity and its molecular explanation is still debated. What is clear though, is that the stabilizing interaction in these systems is understood in terms of electrostatic repulsion via DLVO theory. Recent work [Carpenter et al., PNAS 116 (2019) 9214] has added another element into the discussion, reporting the creation of bare near-zero charged droplets of oil in water that are stable for several days. Key to the creation of the droplets is a rigorous glassware cleaning procedure. Here, we investigate these conclusions and show that the cleaning procedure of glassware has no influence on the electrophoretic mobility of the droplets, that oil droplets with near-zero charge are unstable, and provide an alternative possible explanation for the observations involving glass surface chemistry.

scholarly journals Identification of Cdc37 as a Novel Regulator of the Stress-Responsive Mitogen-Activated Protein Kinase

2003 ◽  
Vol 23 (15) ◽  
pp. 5132-5142 ◽  
Author(s):  
Hisashi Tatebe ◽  
Kazuhiro Shiozaki
Keyword(s):  
Protein Kinase ◽  
Protein Kinases ◽  
Inflammatory Responses ◽  
Cellular Level ◽  
Mitogen Activated Protein Kinase ◽  
Cellular Survival ◽  
Evolutionarily Conserved ◽  
Mitogen Activated Protein ◽  
Extracellular Stimuli ◽  
The Stability

ABSTRACT Eukaryotic cells utilize multiple mitogen-activated protein kinases (MAPKs) to transmit various extracellular stimuli to the nucleus. A subfamily of MAPKs that mediates environmental stress stimuli is also called stress-activated protein kinase (SAPK), which has crucial roles in cellular survival under stress conditions as well as inflammatory responses. Here we report that Cdc37, an evolutionarily conserved kinase-specific chaperone, is a positive regulator of Spc1 SAPK in the fission yeast Schizosaccharomyces pombe. Through a genetic screen, we have identified cdc37 as a mutation that compromises signaling through Spc1 SAPK. The Cdc37 protein physically interacts with Spc1, and the cdc37 mutation affects both the cellular level of the Spc1 protein and stress-induced Spc1 phosphorylation by Wis1 MAPK kinase (MAPKK). Consistently, expression of the stress response genes regulated by the Spc1 pathway is compromised in cdc37 mutant cells. On the other hand, a mutation in Hsp90, which often cooperates with Cdc37 in chaperoning protein kinases, does not affect Spc1 SAPK. These results suggest that Spc1 SAPK is a novel client protein for the Cdc37 chaperone, and the Cdc37 function is important to maintain the stability of the Spc1 protein and to facilitate stress signaling from Wis1 MAPKK to Spc1 SAPK.

scholarly journals Selective regulation of the amount of catalytic subunit of cyclic AMP-dependent protein kinases during isoprenaline-induced growth of the rat parotid gland

1987 ◽  
Vol 248 (1) ◽  
pp. 243-250 ◽  
Author(s):  
G Schwoch
Keyword(s):  
Cyclic Amp ◽  
Dna Synthesis ◽  
Protein Kinases ◽  
Catalytic Subunit ◽  
Regulatory Subunits ◽  
Rat Parotid Gland ◽  
C Subunit ◽  
Dependent Protein ◽  
Rat Parotid ◽  
Stimulation Of

Stimulation of growth of the rat parotid gland by repeated injection of the beta-agonist isoprenaline led to a significant decrease in the activity of cyclic AMP-dependent protein kinases. Immunochemical quantification of the catalytic (C) and regulatory (RI and RII) subunits of the cyclic AMP-dependent protein kinases type I and type II revealed a loss of 65% of the immunochemically measurable amount of catalytic subunit C. The amount of the regulatory subunits, however, remained constant. The observed decrease in C-subunit was not due to a translocation of the molecule to cellular membranes or to an inhibiting effect of the heat-stable inhibitor of cyclic AMP-dependent protein kinases. A selective decrease in only the C-subunit was also observed after a brief exposure to isoprenaline leading to the stimulation of DNA synthesis. Under these conditions, the decrease was observed at the onset of DNA synthesis (17 h after injection), but not at the the time of an earlier small cyclic AMP peak (13 h after injection) or at the time of maximal DNA synthesis (24 h after injection). The results indicate that the amount of the catalytic subunit of cyclic AMP-dependent protein kinases can be regulated independently from that of the regulatory subunits. The time-limited occurrence of the specific change in the amount of the C-subunit suggests that such a regulation is of physiological significance and that it may participate in cyclic AMP-mediated events involved in the control of cellular proliferation.

scholarly journals Antiserum against the catalytic subunit of adenosine 3′:5′-cyclic monophosphate-dependent protein kinase. Reactivity towards various protein kinases

1980 ◽  
Vol 192 (1) ◽  
pp. 223-230 ◽  
Author(s):  
G Schwoch ◽  
A Hamann ◽  
H Hilz
Keyword(s):  
Protein Kinase ◽  
Cyclic Amp ◽  
Protein Kinases ◽  
Rat Liver ◽  
Catalytic Subunit ◽  
Type Ii ◽  
Dependent Protein Kinase ◽  
Subunit C ◽  
Bovine Heart ◽  
Dependent Protein

An antiserum against the catalytic subunit C of cyclic AMP-dependent protein kinase, isolated from bovine heart type II protein kinase, was produced in rabbits. Reaction of the catalytic subunit with antiserum and separation of the immunoglobulin G fraction by Protein A-Sepharose quantitatively removed the enzyme from solutions. Comparative immunotitration of protein kinases showed that the amount of antiserum required to eliminate 50% of the enzymic activity was identical for pure catalytic subunit, and for holoenzymes type I and type II. The reactivity of the holoenzymes with the antiserum was identical in the absence or the presence of dissociating concentrations of cyclic AMP. Most of the holoenzyme (type II) remains intact when bound to the antibodies as shown by quantification of the regulatory subunit in the supernatant of the immunoprecipitate. Titration with the antibodies also revealed the presence of a cyclic AMP-independent histone kinase in bovine heart protein kinase I preparations obtained by DEAE-cellulose chromatography. Cyclic AMP-dependent protein kinase purified from the particulate fraction of bovine heart reacted with the antiserum to the same degree as the soluble enzyme, whereas two cyclic AMP-independent kinases separated from the particle fraction neither reacted with the antiserum nor influenced the reaction of the antibodies with the cyclic AMP-dependent protein kinase. Immunotitration of the protein kinase catalytic subunit C from rat liver revealed that the antibodies had rather similar reactivities towards the rat liver and the bovine heart enzyme. This points to a relatively high degree of homology of the catalytic subunit in mammalian tissues and species. Broad applicability of the antiserum to problems related to cyclic AMP-dependent protein kinases is thus indicated.

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