Search results for "KINASE"

Modulation of protein phosphorylation by natural products

2002

Studies carried out to determine the influence of phosphorylation and dephosphorylation of proteins in a variety of physiological events are of increasing interest. The activity of kinases and phosphatases and their respective inhibition by endogenous mediators and by pharmacological agents regulates a huge number of biochemical pathways involved in cellular proliferation, apoptosis, inflammation, hormonal activity, and gene transcription, amongother processes. This article focuses on the recently described natural products able to interfere negatively with the activity of serine/threonine and tyrosine kinases. These agents are classified, according to theirbiosynthetic origin and chemical …

Properties of locust muscle 6-phosphofructokinase and their importance in the regulation of glycolytic flux during prolonged flight

1987

6-Phosphofructokinase (PFK, EC 2.7.1.11) from the flight muscle of the locust (Locusta migratoria) was purified to a specific activity of 80 μmol min−1 (mg protein)−1 (at 25°C). 1. The enzyme is made up from subunits ofMr-81600, and the smallest catalytically active form is likely to be a tetramer. 2. PFK activity is markedly affected by the pH of the assay; the optimum pH was at about 8. 3. Physiological concentrations of ATP strongly inhibit locust PFK by shifting the S0.5 for fructose 6-phosphate (concentration required for 50% of maximum activity) out of the physiological concentration range. At pH 7.4 and about physiological concentrations of ATP, the curve of PFK activity against the …

Connection between Absorption Properties and Conformational Changes in Deinococcus radiodurans Phytochrome

2014

Phytochromes consist of several protein domains and a linear tetrapyrrole molecule, which interact as a red-light-sensing system. In this study, size-exclusion chromatography and light-scattering techniques are combined with UV-vis spectroscopy to investigate light-induced changes in dimeric Deinococcus radiodurans bacterial phytochrome (DrBphP) and its subdomains. The photosensory unit (DrCBD-PHY) shows an unusually stable Pfr state with minimal dark reversion, whereas the histidine kinase (HK) domain facilitates dark reversion to the resting state. Size-exclusion chromatography reveals that all phytochrome fragments remain as dimers in the illuminated state and dark state. Still, the elut…

DSD-1-Proteoglycan/Phosphacan and Receptor Protein Tyrosine Phosphatase-Beta Isoforms during Development and Regeneration of Neural Tissues

2007

Interactions between neurons and glial cells play important roles in regulating key events of development and regeneration of the CNS. Thus, migrating neurons are partly guided by radial glia to their target, and glial scaffolds direct the growth and directional choice of advancing axons, e.g., at the midline. In the adult, reactive astrocytes and myelin components play a pivotal role in the inhibition of regeneration. The past years have shown that astrocytic functions are mediated on the molecular level by extracellular matrix components, which include various glycoproteins and proteoglycans. One important, developmentally regulated chondroitin sulfate proteoglycan is DSD-1-PG/phosphacan,…

�pfels�urestoffwechsel bei Saccharomyces

1973

1. Aus Saccharomyces cerevisiae St. 79 konnte durch Protamin-und Ammoniumsulfatfallung sowie durch Chromatographie an DEAE-Cellulose ein Malatenzym [l-Malat: NAD(P) Oxidoreduktase, decarboxylierend, E.C. 1.1.1.38 oder 40] angereichert und von Malat-Dehydrogenase (l-Malat: NAD Oxidoreduktase, E.C. 1.1.1.37) weitgehend abgetrennt werden. 2. Neben Mn++-Ionen benotigt das Malatenzym der Hefe NAD oder NADP, bei einem optimalen pH-Wert von 7,5. Es ist spezifisch fur l-Malat, d-Malat wird nicht umgesetzt. Die Enzympraparate decarboxylierten Oxalessigsaure bei Abwesenheit von NAD. 3. Die Km Werte von Malatenzym sind fur l-Malat 5 · 10-2 M, fur NAD 5 · 10-4 M und fur Mangan 1,4 · 10-4 M. 4. Ein Zusa…

2021

The purpose of this study was to investigate blood-based biomarkers and their regulation with regard to different recovery-stress states. A total of 35 male elite athletes (13 badminton, 22 soccer players) were recruited, and two venous blood samples were taken: one in a ‘recovered’ state (REC) after a minimum of one-day rest from exercise and another one in a ‘non-recovered’ state (NOR) after a habitual loading microcycle. Overall, 23 blood-based biomarkers of different physiologic domains, which address inflammation, muscle damage, and tissue repair, were analyzed by Luminex assays. Across all athletes, only creatine kinase (CK), interleukin (IL-) 6, and IL-17A showed higher concentration…

Ibrutinib Abrogates TREM-1 Mediated Neutrophil Activation

2016

Abstract Triggering receptor expressed on myeloid cells 1 (TREM-1) is an activating receptor on neutrophils (PMN) and important in the innate host defence against microbial pathogens. Here we examined the influence of the Bruton tyrosine kinase (BTK) inhibitor ibrutinib on TREM-1 dependent activation of human PMNs. Firstly, ibrutinib specifically inhibited TREM-1 mediated PMN activation of the oxidative burst and CD62L shedding, whereas TLR mediated activation remained unaffected. Correspondingly, ibrutinib suppressed ERK phosphorylation after TREM-1, but not after TLR ligation. To clarify whether this TREM-1 specific effect of ibrutinib was also relevant in vivo, we treated mice with ibrut…

Mechanisms of Resistance to the FLT3-Tyrosine Kinase Inhibitor PKC412 in Patients with AML.

2004

Abstract The FLT3 receptor tyrosine kinase is expressed in 70-90% of cases of AML. Up to 35% of patients with AML show mutations in the JM-region or kinase domain of FLT3. These lead to autophosphorylation promoting ligand-independent cell proliferation and inhibition of apoptosis. Treatment with FLT3 tyrosine kinase inhibitors (TKI) is a promising tool in therapy of AML. Preliminary results investigating the FLT3-TKI PKC412 in patients with relapsed/refractory AML revealed that 11/15 patients (73%) with mutated FLT3 and 16/46 patients (35%) with WT FLT3 showed a >50% blast response in peripheral blood (Estey E et al. Blood.2003; 102:919a). Despite its remarkable efficacy in reducing…

Neurotrophic effects of central nicotinic receptor activation

2000

A growing number of data have shown that compounds interacting with neuronal nicotinic acetylcholine receptors (nAChRs) have, both in vivo and in vitro, the potential to be neuroprotective and that treatment with nAChR agonists elicit long-lasting improvement of cognitive performance in a variety of behavioural tests in rats, monkeys and humans. Epidemiological and clinical studies suggested also a potential neuroprotective/trophic role of (-)-nicotine in neurodegenerative disease, such as Alzheimer's disease and Parkinson's disease. This neuroprotective/trophic role of nAChR activation has been mainly mediated by alpha7 and alpha4beta2 nAChR subtypes, as evidenced using selective nAChR ant…

Cytotoxicity of the Urokinase-Plasminogen Activator Inhibitor Carbamimidothioic Acid (4-Boronophenyl) Methyl Ester Hydrobromide (BC-11) on Triple-Neg…

2015

BC-11 is an easily synthesized simple thiouronium-substituted phenylboronic acid, which has been shown to be cytotoxic on triple negative MDA-MB231 breast cancer cells by inducing a perturbation of cell cycle when administered at a concentration equal to its ED50 at 72 h (117 μM). Exposure of cells to BC-11, either pre-absorbed with a soluble preparation of the N-terminal fragment of urokinase-plasminogen activator (uPa), or in co-treatment with two different EGFR inhibitors, indicated that: (i) BC-11 acts via binding to the N-terminus of the enzyme where uPa- and EGF receptor-recognizing sites are present, thereby abrogating the growth-sustaining effect resulting from receptor binding