Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.7.11.1 (protein kinase)
81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immunohistochemical techniques and antibodies to gamma-aminobutyric acid (GABA), parvalbumin, and cyclic guanosine monophosphate-dependent protein kinase were used to identify populations of cerebellar neurons in culture that exhibit morphological features and immunoreactivity characteristic of neuronal types present in the cortical region of the cerebellum in vivo. The cultures were examined at 3 culture ages: 6-9, 12-15 and greater than 15 days in vitro, reflecting early, intermediate and late periods in cerebellar development. Neurons identified as Purkinje neurons (PNs), granule cells or inhibitory interneurons (stellate, basket, Golgi and Lugaro cells) were present at all culture ages. The granule cells (GCs) and inhibitory interneurons (INs) were morphologically well developed at the youngest culture age studied; morphological features did not change dramatically during the culture period. In contrast, the PNs were morphologically immature at 6-9 DIV (DIV = days in vitro) and exhibited dramatic changes in morphological structure with culture age. Extracellular recordings from PNs. GCs and INs in living cultures revealed that all classes of neurons exhibited spontaneous activity, but that only a portion of the GCs and INs were spontaneously active. The spontaneously active GCs and INs exhibited variable patterns of activity and low firing rates (approximately 2-6 Hz) at all culture ages studied. At 6 DIV, PNs exhibited firing rates and patterns similar to that of the interneurons. At older culture ages, the firing rate and pattern of PNs was significantly different from the GCs and INs and was characterized by high frequency (greater than 10 Hz) spike activity usually in a regular pattern. All cerebellar neurons by excited by the transmitter glutamate (Glu). The Glu response in the GCs and INs consisted of a brief burst of single spikes; in PNs, the response to Glu was prolonged and multiphasic. These data indicate that the cerebellar GCs and INs express morphological, physiological and developmental properties that are significantly different from the PN.
...
PMID:Morphological and physiological properties of rat cerebellar neurons in mature and developing cultures. 290 61

This article summarizes some of our knowledge concerning intracellular protein phosphorylation pathways in nerve cells. It also summarizes, very briefly, recent direct experimental evidence involving intracellular injection of protein kinases, protein kinase inhibitors, and substrates, indicating that protein phosphorylation mediates the actions of a variety of neurotransmitters on their target cells. Finally, it summarizes in somewhat greater detail the results of studies of three different types of substrate proteins that appear to regulate different types of biological responses in nerve cells: synapsin I, a substrate protein present in virtually all nerve terminals, which appears to regulate neurotransmitter release from those nerve terminals; the acetylcholine receptor, the phosphorylation of which regulates its rate of desensitization in the presence of acetylcholine; and DARPP-32, the phosphorylation of which converts it into a very potent phosphoprotein phosphatase inhibitor that may be involved in the regulation by the neuromodulator dopamine of the effects of the neurotransmitter glutamate. The identification and characterization of additional neuronal phosphoproteins can be expected to lead to the clarification of numerous additional molecular mechanisms by which signal transduction is carried out in nerve cells.
...
PMID:Neuronal phosphoproteins. Mediators of signal transduction. 290 93

Independent protein kinases in the synaptic junction (SJ) isolated from rat cerebrum were characterized. SJ showed a protein kinase activity, phosphorylating intrinsic proteins, even in the absence of cyclic AMP or Ca2+ plus calmodulin (CaM) exogenously added. The activity was affected neither by Ca2+ concentrations in the physiological fluctuation range nor by the addition of specific ligands such as glutamate, aspartate, acetylcholine, and concanavalin A. The activity was not due to cyclic AMP-dependent protein kinase in SJ, since the activity was not inhibited by an inhibitor protein for cyclic AMP-dependent protein kinase, and since synapsin I was not specifically phosphorylated whereas cyclic AMP-dependent kinase appeared to phosphorylate selectively the protein in SJ. Phosphorylation of SJ proteins by the independent kinases was about one-third of that of the Ca2+/CaM-dependent protein kinase intrinsic to SJ. The apparent Km for ATP was estimated to be 700 microM. Proteins of 16K Mr and 117K Mr were specifically phosphorylated under the basic condition (in the absence of the substances known to activate specifically protein kinases), as well as six other proteins both under the basic conditions and in the presence of Ca2+ and CaM. The phosphorylation of 150K Mr, 60K Mr, 51K Mr, and 16K Mr SJ proteins was enhanced after prephosphorylation of SJ proteins by intrinsic kinase in the presence of Ca2+ and CaM.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Independent protein kinases associated with the rat cerebral synaptic junction: comparison with cyclic AMP-dependent and Ca2+/calmodulin-dependent protein kinases in the synaptic junction. 303 48

A synthetic random polymer of threonine and glutamate (1:4.4) is readily phosphorylated by protein kinase P but not by five other protein-serine (threonine) kinases. A synthetic random polymer of serine and arginine (1:3) is readily phosphorylated by protein kinase A and protein kinase C but not by protein kinase P. Although the amino acid sequences surrounding the phosphorylated serine (threonine) residue have been demonstrated in studies with small synthetic polypeptides to be decisive factors in the rate at which they are phosphorylated, the findings with the large synthetic polypeptides suggest that in the case of proteins the size, the tertiary structure, and particularly the electrostatic interactions are equally or more important contributing factors. Syringomycin, a toxin from Pseudomonas syringae, and polymyxin B, from Bacillus polymyxa, stimulate protein kinase P, strongly inhibit protein kinase C, and have no effect on protein kinase A. Basic polypeptides with high lysine content are phosphorylated by ATP nonenzymatically.
...
PMID:Phosphorylation of synthetic random polypeptides by protein kinase P and other protein-serine (threonine) kinases and stimulation or inhibition of kinase activities by microbial toxins. 312 47

The specificity of casein kinase II has been further defined by analyzing the kinetics of phosphorylation reactions using a number of different synthetic peptides as substrates. The best peptide substrates are those in which multiple acidic amino acids are present on both sides of the phosphorylatable serine or threonine. Acidic residues on the NH2-terminal side of the serine (threonine) greatly enhance the kinetic constants but are not absolutely required. Acidic residues on the COOH-terminal side of the serine (threonine) are absolutely required. One position for which the occupation of an acidic residue is especially critical is the position located 3 residues to the COOH terminus of the phosphate acceptor site, although the presence of an acidic amino acid in the positions that are 4 or 5 residues removed may also provide an appropriate structure that will serve as a substrate for the kinase. Aspartate serves as a better amino acid determinant than glutamate. A relatively short sequence of amino acids surrounding the phosphate acceptor site appears to serve as the basis for the specificity of casein kinase II. The peptides in this study were also assayed with casein kinase I and the casein kinase from the mammary gland so that the specificities of these kinases could be compared to that of casein kinase II.
...
PMID:Substrate specificity determinants for casein kinase II as deduced from studies with synthetic peptides. 347 30

The increase in the mobilities of neurofilament subunits on SDS-PAGE after dephosphorylation was reversed upon boiling in urea or trifluoroacetylation of lysine epsilon-amino groups. Trifluoroacetylation of native and dephosphorylated neurofilaments also resulted in an overall increase in the phosphorylation of the three subunits by the catalytic subunit of cyclic-AMP-dependent protein kinase. The gel-electrophoretic mobility of neurofilament subunits was also shown to be influenced by carboxylic amino acid residues, as neutralization of these moieties by glycinamidation increased the mobilities of all three subunits on SDS-PAGE. Neurofilament subunits that were both glycinamidated and dephosphorylated had apparent molecular masses of approximately 60 kDa, 112 kDa and 138 kDa. The major sites of these changes in the two largest subunits were shown to be the carboxy-terminal tail domains, which are known to contain high percentages of glutamate. Since interspecies differences in the apparent molecular masses of neurofilament subunits were shown to persist after glycinamidation and dephosphorylation, they appear to be due to differences in polypeptide chain length, rather than glutamate content.
...
PMID:Chemical modification of charged amino acid moieties alters the electrophoretic mobilities of neurofilament subunits on SDS/polyacrylamide gels. 359 91

It has been proposed that the active centre of cyclic AMP-dependent protein kinase contains an arginine-recognition site, which is considered to be essential for the function of the catalytic subunit of the kinase [Matsuo, Huang & Huang (1978) Biochem. J.173, 441-447]. The catalytic subunit can be inactivated by 3-(3-dimethylaminopropyl)-1-ethylcarbodi-imide and glycine ethyl ester at pH6.5. The enzyme can be protected from inactivation by preincubation with histone, a protein substrate of the enzyme. On the other hand, ATP, which also serves as a protein kinase substrate, does not afford protection. Polyarginine, a competitive inhibitor of protein kinase, which is known from kinetic studies to interact specifically with the arginine-recognition site, partially protects the catalytic subunit from inactivation by 3-(3-dimethylaminopropyl)-1-ethylcarbodi-imide. These results lead to the conclusion that the site of modification by carbodi-imide/glycine ethyl ester is most likely located at the arginine-recognition site of the active centre. A value of 1.7+/-0.2 (mean+/-s.d.) mol of carboxy groups per mol of catalytic subunit has been obtained for the number of essential carboxy groups for the function of protein kinase; a complete chemical modification of these essential carboxy groups results in total loss of catalytic activity. Finally, we have identified the essential carboxy group in the catalytic subunit of cyclic AMP-dependent protein kinase as being derived from glutamate residues. This is achieved by a three-step procedure involving an extensive proteolytic digestion of the [1-(14)C]glycine ethyl ester-modified enzyme and two successive high-voltage electrophoreses of the hydrolysate. It is concluded that 1.7mol of glutamyl carboxy groups per mol of catalytic subunit may be considered a component of the arginine-recognition site in the active centre of cyclic AMP-dependent protein kinase.
...
PMID:Modification and identification of glutamate residues at the arginine-recognition site in the catalytic subunit of adenosine 3' :5'-cyclic monophosphate-dependent protein kinase of rabbit skeletal muscle. 624 67

A protein that exhibits greater substrate specificity for cGMP-dependent protein kinase than for cAMP-dependent protein kinase has been purified 8,000-fold from cytosol of rabbit cerebellum to apparent homogeneity as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The protein, termed G-substrate, is a monomer of 23,000 daltons. It is heterogeneous on isoelectric focusing, exhibiting three isoelectric forms over the pH range of 5.2-5.6 cGMP-dependent protein kinase catalyzes the incorporation of 2 mol of phosphate/mol of G-substrate, both into threonine residues. The protein has a high content of aspartate, glutamate, and proline. The hydrodynamic properties, heat stability, and acid solubility of this protein are consistent with an unfolded, nonglobular structure. G-substrate is localized primarily in the cytosol of cerebellum, although low concentrations of a phosphorylated protein with a similar molecular weight are detected in other brain regions.
...
PMID:A specific substrate from rabbit cerebellum for guanosine 3':5'-monophosphate-dependent protein kinase. I. Purification and characterization. 625 70

The role of thyroid hormones in the metabolic adaptation to starvation was investigated in vivo. Glucose production, measured by tracer technique, was enhanced in hyperthyroid (185%) and reduced in hypothyroid (39%) 48-hour starved rats (euthyroid control = 100%). Urinary nitrogen excretion was increased in hyperthyroidism (132%) and decreased in hypothyroidism (70%). Compared with euthyroid controls (=100%) significant alterations for the following regulatory parameters of hepatic gluconeogenesis were observed: 1) tissue cAMP (124%/91%) and protein kinase activation (132%/90%), with a corresponding crossover between pyruvate and P-enolpyruvate (-/+/+/-); 2) pyruvate carboxylase (165%/60%), P-enolpyruvate carboxykinase (140%/82%) and fructose-1.6-bis-P-phosphatase activity (99%/61%), and 3) tissue content of the glucogenic amino acids: alanine (187%/66%) and glutamate (187%/88%), aspartate (179%/68%) and glutamate (137%/75%), as well as of oxaloacetate (254%/66%) and malate (164%/104%). The observed alterations in hepatic oligomycine-sensitive oxygen consumption in hyper- (161%) and hypothyroidism (51%) were related to the measured concentration of the intermediates of the citric acid cycle, the energy state and the mitochondrial redox state. In summary, the different rates of hepatic glucose production in hyper- and hypothyroid starved rats observed in vivo can be ascribed to 1) cAMP content, 2) gluconeogenic key enzyme activities, 3) glucogenic precursor supply and 4) cofactor (ATP) availability.
...
PMID:Starvation-induced changes of hepatic glucose metabolism in hypo- and hyperthyroid rats in vivo. 626 36

DARPP-32 is a neuronal phosphoprotein of Mr = 32,000, originally identified in rat brain (Walaas, S.I., D.W. Aswad, and P. Greengard (1983) Nature 301: 69-72). This protein has now been identified in bovine caudate nucleus cytosol and purified 435-fold to apparent homogeneity as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The purification procedure involved acid extraction at pH 2, CM-cellulose chromatography, DEAE-cellulose chromatography, hydroxylapatite chromatography, and gel filtration on Ultrogel AcA 44. The purified catalytic subunit of cAMP-dependent protein kinase catalyzed the incorporation of 0.96 mol of phosphate/mol of purified DARPP-32. Phosphorylation occurred exclusively on threonine. The isoelectric point of dephospho-DARPP-32 was 4.7, and that of phospho-DARPP-32 was 4.6. The amino acid composition showed a high content of glutamate/glutamine and proline, and a low content of hydrophobic amino acids. DARPP-32 was found to have a Stokes radius of 34 A and a sedimentation coefficient of 2.05 S, indicating that it exists as an elongated monomer.
...
PMID:DARPP-32, a dopamine- and adenosine 3':5'-monophosphate-regulated phosphoprotein enriched in dopamine-innervated brain regions. II. Purification and characterization of the phosphoprotein from bovine caudate nucleus. 631 28


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---