scholarly journals Characteristics of polyamine stimulation of cyclic nucleotide-independent protein kinase reactions

1985 ◽  
Vol 232 (3) ◽  
pp. 767-771 ◽  
Author(s):  
K Ahmed ◽  
S A Goueli ◽  
H G Williams-Ashman
Keyword(s):  
Catalytic Activity ◽  
Protein Kinase ◽  
Protein Kinases ◽  
Nuclear Protein ◽  
Direct Stimulation ◽  
Protein Substrate ◽  
Protein Substrates ◽  
Effects Of Temperature ◽  
Independent Protein ◽  
Stimulation Of

The extent of direct stimulation by spermine of reactions catalysed by nuclear N1 and N2 protein kinases purified from liver and prostate depends critically on the nature of the protein substrate. The chemically inert Co(NH3)36+ ion exerts effects on protein kinase reactions similar to those of spermidine or spermine. This enhancement of the phosphorylation of various protein substrates by polyamines or Co(NH3)63+ by purified nuclear protein kinase preparations was studied in relation to effects of temperature, pH and other factors. The results provide further support for our hypothesis [Ahmed, Wilson, Goueli & Williams-Ashman (1978) Biochem. J. 176, 739-750] that the enhancement of certain protein kinase reactions by polycations relates primarily to their interaction with the protein substrate, yielding more favourable conformations for phosphorylation by the protein kinase, rather than a direct effect on its catalytic activity.

Rat histidine decarboxylase promoter is regulated by gastrin through a protein kinase C pathway

1996 ◽  
Vol 270 (4) ◽  
pp. G619-G633 ◽  
Author(s):  
M. Hocker ◽  
Z. Zhang ◽  
D. A. Fenstermacher ◽  
S. Tagerud ◽  
M. Chulak ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Time Course ◽  
Histidine Decarboxylase ◽  
Peptide Hormone ◽  
Direct Stimulation ◽  
Gastric Glands ◽  
Kinase C ◽  
Translational Start ◽  
Stimulation Of

The enzyme L-histidine decarboxylase (HDC; EC 4.1.1.22), which converts L-histidine to histamine, plays a key role in the regulation of acid secretion. In the rat and human stomach, the peptide hormone gastrin appears to be one of the main regulators of HDC expression. In rats, marked elevation of gastric HDC mRNA abundance was observed within 12 h after induction of hypergastrinemia by a single injection of the proton-pump blocker omeprazole. In situ hybridization revealed that HDC expression occurred in the basal third of gastric glands where enterochromaffin-like cells are localized. To study the regulation of HDC gene transcription, 1,291 nucleotides of the 5'-flanking region of the rat HDC gene and the noncoding portion of exon 1 were cloned and sequenced. Gastrin and cholecystokinin (CCK) octapeptide equipotently stimulated the transcriptional activity of the rat HDC promoter three- to fourfold, and deletion analysis revealed the presence of a gastrin response element within 201 nucleotides upstream of the translational start site. Time-course studies revealed maximal activation of the HDC promoter after 12-36 h. Direct stimulation of protein kinase C (PKC) with the phorbol ester phorbol 12-myristate 13-acetate (PMA) substantially elevated rat HDC promoter activity, whereas induction of Ca2+ -dependent signaling pathways with thapsigargin was without effect. Downregulation or blockade of PKC abolished the effects of gastrin and PMA on the HDC promoter. These data indicate that stimulation of the CCK-B/gastrin receptor activates the rat HDC promoter in a time- and dose-dependent fashion and that this effect is primarily mediated via a PKC-dependent signaling pathway. Use of HDC as a model gene will allow further investigation of the intracellular pathways that are involved in gastrin-dependent gene regulation.

scholarly journals Nuclear protein kinase CLK1 uses a non-traditional docking mechanism to select physiological substrates

2015 ◽  
Vol 472 (3) ◽  
pp. 329-338 ◽  
Author(s):  
Malik M. Keshwani ◽  
Kendra L. Hailey ◽  
Brandon E. Aubol ◽  
Laurent Fattet ◽  
Maria L. McGlone ◽  
...  
Keyword(s):  
Cell Division ◽  
Protein Kinase ◽  
Nuclear Protein ◽  
Cell Division Cycle ◽  
Protein Substrates ◽  
Docking Mechanism ◽  
Physiological Substrates

CLK1 (Cdc (cell division cycle)2-like kinase 1) uses an oligomerization mechanism to recognize its physiological protein substrates.

scholarly journals Insulin directly stimulates mitochondrial glucose oxidation in the heart

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Qutuba G. Karwi ◽  
Cory S. Wagg ◽  
Tariq R. Altamimi ◽  
Golam M. Uddin ◽  
Kim L. Ho ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Glucose Uptake ◽  
Glucose Oxidation ◽  
Glycogen Synthase ◽  
Acid Oxidation ◽  
Mouse Heart ◽  
Insulin Stimulation ◽  
Direct Stimulation ◽  
Gsk 3Β ◽  
Stimulation Of

Abstract Background Glucose oxidation is a major contributor to myocardial energy production and its contribution is orchestrated by insulin. While insulin can increase glucose oxidation indirectly by enhancing glucose uptake and glycolysis, it also directly stimulates mitochondrial glucose oxidation, independent of increasing glucose uptake or glycolysis, through activating mitochondrial pyruvate dehydrogenase (PDH), the rate-limiting enzyme of glucose oxidation. However, how insulin directly stimulates PDH is not known. To determine this, we characterized the impacts of modifying mitochondrial insulin signaling kinases, namely protein kinase B (Akt), protein kinase C-delta (PKC-δ) and glycogen synthase kinase-3 beta (GSK-3β), on the direct insulin stimulation of glucose oxidation. Methods We employed an isolated working mouse heart model to measure the effect of insulin on cardiac glycolysis, glucose oxidation and fatty acid oxidation and how that could be affected when mitochondrial Akt, PKC-δ or GSK-3β is disturbed using pharmacological modulators. We also used differential centrifugation to isolate mitochondrial and cytosol fraction to examine the activity of Akt, PKC-δ and GSK-3β between these fractions. Data were analyzed using unpaired t-test and two-way ANOVA. Results Here we show that insulin-stimulated phosphorylation of mitochondrial Akt is a prerequisite for transducing insulin’s direct stimulation of glucose oxidation. Inhibition of mitochondrial Akt completely abolishes insulin-stimulated glucose oxidation, independent of glucose uptake or glycolysis. We also show a novel role of mitochondrial PKC-δ in modulating mitochondrial glucose oxidation. Inhibition of mitochondrial PKC-δ mimics insulin stimulation of glucose oxidation and mitochondrial Akt. We also demonstrate that inhibition of mitochondrial GSK3β phosphorylation does not influence insulin-stimulated glucose oxidation. Conclusion We identify, for the first time, insulin-stimulated mitochondrial Akt as a prerequisite transmitter of the insulin signal that directly stimulates cardiac glucose oxidation. These novel findings suggest that targeting mitochondrial Akt is a potential therapeutic approach to enhance cardiac insulin sensitivity in condition such as heart failure, diabetes and obesity.

scholarly journals Identifying and characterizing casein kinase II in human platelets

Blood ◽  
1994 ◽  
Vol 83 (12) ◽  
pp. 3517-3523 ◽  
Author(s):  
CH Hoyt ◽  
CJ Oh ◽  
JB Beekman ◽  
DW Litchfield ◽  
KM Lerea
Keyword(s):  
Protein Kinase ◽  
Protein Kinases ◽  
Casein Kinase Ii ◽  
Human Platelets ◽  
Casein Kinase ◽  
Immunogold Electron Microscopy ◽  
Beta Subunits ◽  
Specific Substrate ◽  
Substrate Peptide ◽  
Independent Protein

Abstract We have recently shown that inhibition of protein phosphatases in platelets causes increases in protein phosphorylations with a concomitant inhibition of platelet responses. The burst in protein phosphorylation appears to be catalyzed by messenger-independent protein kinases. The aim of the present study was to characterize the presence of broad families of protein kinases found in platelets. Lysates of control and thrombin-stimulated platelets were prepared, and proteins were separated on MONO Q fast protein liquid chromatography. In addition to the presence of histone protein kinase and tyrosine kinase activities, human platelets contain casein kinase II (CKII) activity as assessed by phosphorylation of a specific substrate peptide. Western blot analysis and immunogold electron microscopy studies further showed the presence of alpha-, alpha'-, and beta- subunits of CKII. The enzyme appears to be distributed throughout the cytosol and not secreted after thrombin treatment. Immunoprecipitation studies suggest that at least some of the holoenzymes exist as an alpha alpha' beta 2 complex. Although no activation of the enzyme was detected after thrombin treatment, our results show that CKII is a major messenger-independent protein kinase in platelets.

Adenosine A1 receptor-mediated inhibition of myocardial norepinephrine release involves neither phospholipase C nor protein kinase C but does involve adenylyl cyclase

2006 ◽  
Vol 84 (5) ◽  
pp. 573-577 ◽  
Author(s):  
Frank Schütte ◽  
Christof Burgdorf ◽  
Gert Richardt ◽  
Thomas Kurz
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Adenylyl Cyclase ◽  
Phospholipase C ◽  
Suppressive Effect ◽  
Inhibitory Effect ◽  
Direct Stimulation ◽  
Kinase C ◽  
Gf 109203X ◽  
Stimulation Of

Stimulation of adenosine A1 receptors in the heart exerts cardioprotective effects by inhibiting norepinephrine (NE) release from sympathetic nerve endings. The intraneuronal signal transduction triggered by presynaptic adenosine A1 receptors is still not completely understood. The objective of the present study was to determine whether phospholipase C (PLC), protein kinase C (PKC), and adenylyl cyclase (AC) are involved in the adenosine A1 receptor-mediated inhibition of endogenous (stimulation-induced) NE release in isolated Langendorff-perfused rat hearts as an approach to elucidate their role in the cardiovascular system. Activation of adenosine A1-receptors with 2-chloro-N6-cyclopentyladenosine (CCPA) decreased cardiac NE release by ~40%. Inhibition of PLC with 1-[6-[[(17b)-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione (U 73122) as well as inhibition of PKC with 2-[1-(3-dimethylaminopropyl)indol-3-yl]-3-(indol-3-yl)maleimide (GF 109203X) slightly but significantly decreased NE release; however, the suppressive effect of CCPA on NE release was not modulated by U 73122 or GF 109203X. Blockade of AC with 9-(tetrahydro-2′-furyl)adenine (SQ 22536) reversed the inhibitory effect of CCPA on sympathetic neurotransmitter release irrespective of whether PKC was pharmacologically activated by phorbol 12-myristate 13-acetate or was not activated, indicating a PKC-independent but AC-dependent mechanism. Direct stimulation of AC with forskolin increased NE release by ∼20%; an effect that was antagonized by either CCPA or SQ 22536. These data suggest that the adenosine A1 receptor-mediated inhibition of NE release does not involve PLC or PKC but does involve AC.

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