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1.
The 130 kDa atrial natriuretic factor receptor (ANF-R1) purified from bovine adrenal zona glomerulosa is phosphorylated in vitro by serine/threonine protein kinases such as cAMP-, cGMP-dependent and protein kinase C. This phosphorylation is independent of the presence of ANF (99–126) and there is no detectable intrinsic kinase activity associated with the ANF-R1 receptor or with its activated form. In bovine adrenal zona glomerulosa cells, TPA (phorbol ester) induces a marked inhibition of the ANF-stimulated cGMP accumulation as well as of the membrane ANF-sensitive guanylate cyclase catalytic activity without any change in the binding capacity or affinity for 125I-ANF. However, we have demonstrated a significant 32P incorporation in the ANF-R1 receptor of the TPA-treated cells. The effect of TPA on the zona glomerulosa ANF-R1 receptors was abolished by calphostin C, a specific protein kinase C inhibitor. Altered ANF actions due to blunted response of guanylate cyclase to ANF could be a consequence of the ANF receptor phosphorylation by excessive activity of protein kinase C and might be involved in the pathogenesis of hypertension.Abbreviations ANF
Atrial Natriuretic Factor
- ANF-R1
Atrial Natriuretic Factor Receptor, subtype 1
- ATP
Adenosine Triphosphate
- CaCl2
Calcium Chloride
- cAMP
Adenosine cyclic 3,5-Monophosphate acid
- cGMP
Guanosine cyclic 35-Monophosphate acid
- EDC
1-Ethyl-3-[3-Dimethylaminopropyl] Carbodiimide
- EDTA
Ethylenediaminetetraacetic Acid
- GTP
Guanosine Triphosphate
- IBMX
3-isobutyl-1-methylxanthine
- kDa
Kilodaltons
- MgCl2
Magnesium Chloride
- MgAC
Magnesium Acetate
- NaCl
Sodium Chloride
- PAGE
Polyacrylamide Gel Electrophoresis
- PKA
cAMP-dependent protein kinase
- PKG
cGMP-dependent Protein Kinase
- PKC
Calcium/Phospholipid-dependent Protein Kinase
- RIA
Radioimmunoassay
- SDS
Sodium Dodecyl Sulfate
- SHR
Spontaneously Hypertensive Rat
- Tris HCl
Tris (Hydroxymethyl) aminomethane Hydrochloride
- TPA
12-O-Tetradecanoyl-Phorbol-13-Acetate 相似文献
2.
Homoserine kinase is a potential control point in the biosynthetic pathway for threonine, isoleucine and methionine. The radish leaf enzyme was tested 相似文献
3.
Effects of the Phosphatase Inhibitors Calyculin A and Okadaic Acid on Acetylcholine Synthesis and Content of Rat Hippocampal Formation 总被引:2,自引:2,他引:0
Abstract: The biochemical mechanisms involved in the regulation of acetylcholine (ACh) turnover are poorly understood. In the experiments reported here, we examined whether inhibition of the serine/threonine phosphatases 1 and 2A by calyculin A or okadaic acid alters ACh synthesis by rat hippocampal preparations. With hippocampal slices, calyculin A (50 n M ) and okadaic acid (50 n M ) reduced significantly ( p < 0.01) the synthesis of [3 H]ACh from [3 H]choline. Both calyculin A and okadaic acid produced significant depletion of endogenous tissue ACh in a concentration-dependent manner ( p < 0.01). This depletion was not the result of a drug-induced increase of spontaneous ACh release, which was not changed significantly ( p > 0.7) by either drug. Choline acetyltransferase (ChAT) activity from tissue exposed to calyculin A or okadaic acid was reduced in a concentration-dependent manner ( p < 0.05), but these phosphatase inhibitors did not act directly on ChAT in vitro; i.e., enzymatic activity was not altered significantly ( p > 0.4) in the presence of calyculin A or okadaic acid. Both high-affinity and low-affinity [3 H]choline uptake by hippocampal synaptosomes were reduced significantly in a concentration-dependent manner in the presence of calyculin A or okadaic acid; these agents reduced V max values for high- and low-affinity choline uptake ( p < 0.01) with no significant change in K m values ( p > 0.1), indicating a noncompetitive inhibition. Taken together, these data suggest that phosphatase activity plays a role in presynaptic central cholinergic nerve terminal function, in particular in the modulation of ACh synthesis. 相似文献
4.
In a previous report [Yanget al., (1987a),J. Biol Chem.
262, 7034–7040], a cyclic-AMP- and calcium-independent brain kinase which requires autophosphorylation for activity was identified as a very potent myelin basic protein (MBP) kinase. In this report, the phosphorylation sites of MBP by this autophosphorylation-dependent protein kinase (autokinase) are further determined by two-dimensional electrophoresis/thin-layer chromatography, phosphoamino acid analysis, high-performance liquid chromatography, tryptic peptide mapping, sequential manual Edman degradation, and direct peptide sequencing. Autokinase phosphorylates MBP on both threonine and serine residues. Three major tryptic phosphopeptide peaks were resolved by C18-reversed phase highper-formance liquid chromatography. Sequential manual Edman degradation together with direct sequence analysis revealed that FS(p)WGAEGQKPGFGYGGR is the phosphorylation site sequence (molar ratio 1.0) for the first major phosphopeptide peak. When mapping with bovine brain MBP sequence, we finally demonstrate Ser115, one of thein vivo phosphorylation sites in MBP, as the major site phosphorylated by autokinase, implicating a physiologically relevant role of autokinase in the regulation of brain myelin function. By using the same approach, we also identified HRDT(p)GILDSLGR (molar ratio 0.9) and TT(p)HYGSLPQK (molar ratio 0.8) as the major phosphorylation site sequences in32P-MBP phosphorylated by autokinase, further indicating that -Arg-XSer/Thr-(neutral amino acid)3-(amino acid-containing hydroxyl group such as Ser/Glu/Asp)-(neutral amino acid)2-may represent a unique consensus sequence motif specifically recognized by this autophosphorylation-dependent multisubstrate/ multifunctional protein kinase in the brain. 相似文献
5.
6.
Sabine J. Rundle Andrew J. Hartung John W. Corum III Michael O'Neill 《Plant molecular biology》1995,28(2):257-266
Type 2A serine/threonine protein phosphatases (PP2A) are key components in the regulation of signal transduction and control of cell metabolism. The activity of these protein phosphatases is modulated by regulatory subunits. While PP2A activity has been characterized in plants, little is known about its regulation. We used the polymerase chain reaction to amplify a segment of a cDNA encoding the B regulatory subunit of PP2A from Arabidopsis. The amplified DNA fragment of 372 nucleotides was used as a probe to screen an Arabidopsis cDNA library and a full-length clone (AtB) of 2.1 kbp was isolated. The predicted protein encoded by AtB is 43 to 46% identical and 53 to 56% similar to its yeast and mammalian counterparts, and contains three unique regions of amino acid insertions not present in the animal B regulatory subunit. Genomic Southern blots indicate the Arabidopsis genome contains at least two genes encoding the B regulatory subunit. In addition, other plant species also contain DNA sequences homologous to the B regulatory subunit, indicating that regulation of PP2A activity by the 55 kDa B regulatory subunit is probably ubiquitous in plants. Northern blots indicate the AtB mRNA accumulates in all Arabidopsis tissues examined, suggesting the protein product of the AtB gene performs a basic housekeeping function in plant cells. 相似文献
7.
Crystallization and preliminary crystallographic analysis of recombinant human P38 MAP kinase.
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S. Pav D. M. White S. Rogers K. M. Crane C. L. Cywin W. Davidson J. Hopkins M. L. Brown C. A. Pargellis L. Tong 《Protein science : a publication of the Protein Society》1997,6(1):242-245
The recombinant human p38 MAP kinase has been expressed and purified from both Escherichia coli and SF9 cells, and has been crystallized in two forms by the hanging drop vapor diffusion method using PEG as precipitant. Both crystal forms belong to space group P2(1)2(1)2(1). The cell parameters for crystal form 1 are a = 65.2 A, b = 74.6 A and c = 78.1 A. Those for crystal form 2 are a = 58.3 A, b = 68.3 A and c = 87.9 A. Diffraction data to 2.0 A resolution have been collected on both forms. 相似文献
8.
Previous experience with the Langevin/implicit-Euler scheme for dynamics (“LI”) on model systems (butane, water) has shown that LI is numerically stable for timesteps in the 5–20 fs range but quenches high-frequency modes. To explore applications to polypeptides, we apply LI to model systems (several dipeptides, a tetrapeptide, and a 13-residue oligoalanine) and also develop a new dynamics driver approach (“DA”). The DA scheme, based on LI, addresses the important issue of proper sampling, which is unlikely to be solved by small-time step integration methods or implicit methods with intrinsic damping at room temperature, such as LI. Equilibrium averages, time-dependent molecular properties, and sampling trends at room temperature are reported for both LI and DA dynamics simulations, which are then compared to those generated by a standard explicit discretization of the Langevin equation with a 1 fs timestep. We find that LI's quenching effects are severe on both the fast and slow (due to vibrational coupling) frequency modes of all-atom polypeptides and lead to more restricted dynamics at moderate timesteps (40 fs). The DA approach empirically counteracts these damping effects by adding random atomic perturbations to the coordinates at each step (before the minimization of a dynamics function). By restricting the energetic fluctuations and controlling the kinetic energy, we are able with a 60 fs timestep to generate continuous trajectories that sample more of the relevant conformational space and also reproduce reasonably Boltzmann statistics. Although the timescale for transition may be accelerated by the DA approach, the transitional. information obtained for the alanine dipeptide and the tetrapeptide is consistent with that obtained by several other theoretical approaches that focus specifically on the determination of pathways. While the trajectory for oligoalanine by the explicit scheme over the nanosecond timeframe remains in the vicinity of the full αR-helix starting structure, and a high-temperature (6000°K) MD trajectory departs slowly from the a helical structure, the DA-generated trajectory for the same CPU time exhibits unfolding and refolding and reveals a range of conformations with an intermediate helix content. Significantly, this range of states is more consistent with spectroscopic experiments on small peptides, as well as the cooperative two-state model for helix–coil transition. The good, near-Boltzmann statistics reported for the smaller systems above, in combination with the interesting oligoalanine results, suggest that DA is a promising tool for efficiently exploring conformational spaces of biomolecules and exploring folding/unfolding processes of polypeptides. © 1995 Wiley-Liss, Inc. 相似文献
9.
Summary Diets containing 8 or 15% protein from casein plus limiting amino acids, 25% fat and adequate levels of other nutrients for rat growth were supplemented with 0, 0.5, 1.0, 2.0 or 4% of excess L-threonine. Addition of up to 1% excess threonine had little effect on weight gains or food intakes of weanling rats, but addition of 2 and 4% threonine caused a drastic reduction in weight gains or food intakes (up to 41%); the adverse effect being more severe in rats fed lower protein diets. Addition of graded levels of excess threonine resulted in (5 to 47-fold and 4 to 20-fold) increase in concentration of free threonine in rat plasma and brain, respectively. Addition of excess threonine also caused up to 5-fold increase in plasma level of 3-methylhistidine, suggesting increased muscle protein breakdown. 相似文献
10.
D Mark-Malchoff G V Marinetti J D Hare A Meisler 《Biochemical and biophysical research communications》1977,75(3):589-597
Analysis of the lipids of normal hamster embryo fibroblasts and polyoma virus transformed fibroblasts shows a decrease in phosphatidylcholine and phosphatidylethanolamine and a marked increase in a threonine phospholipid after transformation. Transformed cells also react differently with fluorodinitrobenzene and trinitrobenzenesulfonate. phosphatidylethanolamine of transformed cells reacts to a greater extent with both probes. Phosphatidylserine and the threonine phospholipid of both cells do not react with trinitrobenzenesulfonate. The threonine phospholipid is provisionally identified as phosphatidylthreonine. 相似文献