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)

In situ hybridization histochemistry, using cRNA probes, revealed a complementarity in the distributions of cells in the basal ganglia, basal nucleus of Meynert, thalamus, hypothalamus, and rostral part of the midbrain that showed gene expression for glutamic acid decarboxylase (GAD) or the alpha-subunit of type II calcium-calmodulin-dependent protein kinase (CAM II kinase-alpha). Cells in certain nuclei such as the thalamic reticular nucleus, globus pallidus, and pars reticulata of the substantia nigra show GAD gene expression only; others in nuclei such as the basal nucleus of Meynert, medial mamillary nuclei, and ventromedial hypothalamic nuclei show CAM II kinase-alpha gene expression only. A few nuclei, for example, the pars compacta of the substantia nigra and the greater part of the subthalamic nucleus, display gene expression for neither GAD nor CAM II kinase-alpha. In other nuclei, notably those of the dorsal thalamus, and possibly in the striatum, GAD- and CAM II kinase-expressing cells appear to form two separate populations that, in most thalamic nuclei, together account for the total cell population. In situ hybridization reveals large amounts of CAM II kinase-alpha mRNA in the neuropil of most nuclei containing CAM II kinase-alpha-positive cells, suggesting its association with dendritic polyribosomes. The message may thus be translated at those sites, close to the synapses with which the protein is associated. The in situ hybridization results, coupled with those from immunocytochemical staining for CAM II kinase-alpha protein, indicate that CAM II kinase-alpha is commonly found in certain non-GABAergic afferent fiber systems but is not necessarily present in the postsynaptic cells on which they terminate. It appears to be absent from most GABAergic fiber systems but can be present in the cells on which they terminate. This suggests that the kinase may be differentially engaged in pre- and postsynaptic functions at certain synapses.
...
PMID:Differential gene expression for glutamic acid decarboxylase and type II calcium-calmodulin-dependent protein kinase in basal ganglia, thalamus, and hypothalamus of the monkey. 164 94

In preparations of synaptic terminals (synaptosomes) isolated from rat brain, the activity of phospholipase A2 (PLA2), a phospholipid hydrolase that serves a central function in signal transduction, was inhibited in a Ca(2+)-dependent manner by incubation with 60 mM K+ or with the Ca(2+)-selective ionophore ionomycin. Reversal by alkaline phosphatase treatment suggested that this inhibitory effect resulted from phosphorylation of a synaptosomal protein substrate. When lysed synaptosomes were incubated with Ca2+/calmodulin (CaM), purified Ca2+/CAM-dependent protein kinase II (Ca2+/CaM-dependent PK II) and ATP, PLA2 activity in lysates was nearly abolished within 10 min. This effect was accompanied by a marked decrease in the Vmax of the enzyme and little or no change in the Km. Furthermore, Ca2+/CaM with ATP but without exogenous Ca2+/CaM-dependent PK II partially inhibited PLA2 activity, and this effect was prevented by treating the lysates with a selective peptide inhibitor of Ca2+/CaM-dependent PK II. In contrast, incubation of intact synaptosomes with 4 beta-phorbol 12-myristate 13-acetate or of lysed synaptosomes with purified protein kinase C had little or no effect on PLA2 activity. The results strongly suggest that the Ca(2+)-dependent inhibition of PLA2 activity observed in intact nerve endings was produced by activation of the multifunctional Ca2+/CaM-dependent PK II. A membrane-permeable adenylyl cyclase activator, forskolin, enhanced PLA2 activity in intact synaptosomes, and cAMP-dependent protein kinase potentiated PLA2 activity in lysed synaptosomes. Furthermore, another broad-spectrum protein kinase present in synaptic terminals, casein kinase II, also potentiated PLA2 activity in lysed synaptosomes. The effects of both protein kinases were associated with a decrease in Km and no change in Vmax. The results suggest that PLA2 activity in synaptic terminals is subject to bidirectional control by distinct signal transduction pathways. Moreover, mutually antagonistic effects of the Ca2+/CaM-dependent PK II and PLA2 pathways provide a possible molecular mechanism for bidirectional modulation of neurotransmitter release.
...
PMID:Bidirectional control of phospholipase A2 activity by Ca2+/calmodulin-dependent protein kinase II, cAMP-dependent protein kinase, and casein kinase II. 165 Apr 81

Transformation of cultured chick lens epithelial cells with a temperature-sensitive mutant of Rous sarcoma virus (tsRSV) leads to radical changes in cell shape and interactions. When cultured at the restrictive temperature (42 degrees C), the transformed cells largely retained epithelial morphology and intercellular adherens junctions (AJ), whereas on switch to the permissive temperature (37 degrees C) they rapidly became fibroblastoid, their AJ deteriorated, and cell adhesion molecules (A-CAM) (N-cadherin) largely disappeared from intercellular contact sites. The microfilament system that was primarily associated with these junctions was markedly rearranged on shift to 37 degrees C and remained associated mainly with cell-substrate focal contacts. These apparent changes in intercellular AJ were not accompanied by significant alterations in the cellular content of several junction-associated molecules, including A-CAM, vinculin, and talin. Immunolabeling with phosphotyrosine-specific antibodies indicated that both cell-substrate and intercellular AJ were the major cellular targets for the pp60v-src tyrosine-specific protein kinase. It was further shown that intercellular AJ components serve as substrates to tyrosine kinases also in nontransformed lens cells, because the addition of a combination of vanadate and H2O2--which are potent inhibitors of protein tyrosine phosphatases--leads to a remarkable accumulation of immunoreactive phosphotyrosine-containing proteins in these junctions. This finding suggests that intercellular junctions are major sites of action of protein tyrosine kinases and that protein tyrosine phosphatases play a major role in the regulation of phosphotyrosine levels in AJ of both normal and RSV-transformed cells.
...
PMID:Modulation of intercellular adherens-type junctions and tyrosine phosphorylation of their components in RSV-transformed cultured chick lens cells. 165 May 81

The actions of ethanol on kinase stimulated phosphorylation were examined using highly purified protein kinases and a variety of purified substrates. Ethanol (25-200 mM) failed to alter the phosphorylation of histone IIa and histone IIIs by cAMP-dependent protein kinase (PKA) and protein kinase C (PKC), respectively. Moreover, ethanol (25-200 mM) did not affect the phosphorylation of synapsin I by Ca(2+)-calmodulin-dependent protein kinase II (CAM kinase II). Finally, neither PKA nor PKC stimulated phosphorylation of the GABAA receptor (GABAA-R) was modulated by ethanol at any concentration of ethanol tested. These results suggest that ethanol, in pharmacological concentrations, has no direct actions on the ability of these kinases to catalyze the phosphorylation of specific substrate proteins. In particular, ethanol does not appear to directly influence GABAA-R phosphorylation by either PKA or PKC.
...
PMID:Ethanol has no effect on cAMP-dependent protein kinase-, protein kinase C-, or Ca(2+)-calmodulin-dependent protein kinase II-stimulated phosphorylation of highly purified substrates in vitro. 166 14

We purified a Ca2+/calmodulin (CaM)-dependent protein kinase (CaM kinase) from the yeast Saccharomyces cerevisiae with properties similar to mammalian type II CaM kinases. Degenerate oligonucleotides designed on the basis of the amino acid sequence of tryptic peptides from the 55 kd subunit of the yeast CaM kinase were used to isolate its gene from a set of lambda gt11-yeast genomic DNA phage clones initially selected by the ability to bind 125I-labelled yeast CaM. The cloned gene (CMK1) encodes an open reading frame that is homologous to the sequences of vertebrate type II CaM kinases. Several criteria demonstrated that the CMK1 gene product is the 55 kd polypeptide. Neither over-production (11-fold) nor complete elimination of the CMK1 gene product had any detectably deleterious effect on yeast cell growth. Extracts from cmk1 delta cells, which lacked detectable p55 using an antiserum raised against a Staphylococcus aureus protein A-CMK1 fusion protein, possessed significant residual Ca2+/CAM-dependent protein kinase activity. Using the CMK1 gene as a probe at low stringency, a second gene (CMK2) encoding another CaM-dependent protein kinase with striking sequence similarity to CMK1 was cloned. Deletion of CMK2, or both CMK1 and CMK2, was not lethal, although loss of CMK2 caused a slow rate of spore germination.
...
PMID:Multiple Ca2+/calmodulin-dependent protein kinase genes in a unicellular eukaryote. 202 47

The major neuronal populations of the primate cerebral cortex can be classified immunocytochemically according to their transmitters and in terms of the differential expression of certain other molecules such as neuropeptides, calcium-binding proteins and protein kinases. We have been able to chart the time course of developmental expression of these molecules and to show that gene expression for many of them is regulated in adult and infant animals by afferent activity entering the cortex. In the visual cortex of adult monkeys, levels of immunocytochemically detectable gamma aminobutyric acid (GABA), of its synthesizing enzyme glutamic acid decarboxylase (GAD) and of the tachykinins are greatly reduced in deprived ocular dominance columns within 24 h of blocking impulse activity in the optic nerve by intraocular injection of tetrodotoxin (TTX). Conversely, levels of immunocytochemically detectable calcium-calmodulin-dependent protein kinase (CAMII kinase) are increased in deprived eye dominance columns. These effects are quickly reversible on restoration of binocular vision, and experiments involving in situ hybridization and S1 nuclease protection assays show that the changes are associated with parallel changes in mRNA levels for preprotachykinin and CAM II kinase, but not for GAD, which appears to be regulated by post-transcriptional mechanisms. Experiments in the primate somatic sensory cortex suggest comparable activity-dependent effects on gene expression there also. It is proposed that effects of this type underlie the establishment of cortical maps during development and their activity-dependent mutability in adulthood.
...
PMID:The role of afferent activity in the maintenance of primate neocorticalfunction. 217 67

In our previous report we showed cytochrome b5 to be a competitive inhibitor of cAMP-dependent protein kinase (PKA) for interaction with cytochrome P450 (P450). While P450 was phosphorylated, cytochrome b5 was not. The phosphorylation of P450 resulted in an inhibition of its catalytic activity. In this report we attempt to determine the relationship between phosphorylation of P450 from phenobarbital-induced rat and its destruction. The results indicate there is a considerable alteration of P450 IIB1 when it is put into the phosphorylation medium. This includes destruction, i.e., loss of the hemoprotein nature (Soret peak), as well as denaturation, conversion of a proportion of the P450 to P420. The extent of phosphorylation correlated best with the amount of destroyed hemoprotein, and not with the formation of P420. There did not appear to be phosphorylation-dependent formation of apo-P450. Further, prior conversion of the P450 to P420 using sodium deoxycholate showed the same extent of phosphorylation as before the conversion. Thus, intact P450 is not required for phosphorylation nor is phosphorylation a prerequisite for hemoprotein destruction. P450 CAM (CIA1), which has the PKA substrate recognition sequence internalized, likewise undergoes conversion to P420 but this denaturation does not result in phosphorylation. Destruction of CIA1 with 6 M urea, however, did permit phosphorylation by PKA. P450 IIB1 destruction was greatly diminished by cytochrome b5. This stabilization resulted in a decreased degree of phosphorylation as well as an increase in negative ellipticity in circular dichroism, indicative of an increase in the proportion of alpha-helical content in the P450. Suggestions are made that this structural modification caused by cytochrome b5 stabilizes the P450 against denaturation as well as against destruction and phosphorylation. Further, when the P450 IIB1 was kept stable as P450 in the absence of cytochrome b5 and without loss of hemoprotein during the incubation period, using phosphate-glycerol buffer containing 0.4% Emulgen 911, the phosphorylation of the P450 was greatly diminished, with only minor effects on the protein kinase reaction itself. These results suggest that the protein kinase reaction itself. These results suggest that the protein kinase substrate recognition sequence is not readily accessible to PKA in mammalian P450 IIB1 but requires a destabilization of the protein for phosphorylation to take place.
...
PMID:Relationship between phosphorylation and cytochrome P450 destruction. 227 44

The neural cell-adhesion molecule (N-CAM) is detected as at least 3 related polypeptides generated by alternative splicing of a single gene. In vivo the 2 larger polypeptides are phosphorylated, but the smallest polypeptide, which lacks a cytoplasmic domain, is not. We have found that the 2 larger polypeptides are phosphorylated in vivo on several common phosphorylation sites. Furthermore, the largest polypeptide has additional sites, suggesting that some phosphorylation occurs in that portion of the intracellular region unique to it. In vitro N-CAM is not a substrate for cyclic AMP-dependent protein kinase, cyclic GMP-dependent protein kinase, calcium/calmodulin-dependent protein kinase I, II, or III, protein kinase C, or casein kinase II. However, we have isolated 2 protein kinases from mammalian and avian brain that phosphorylate rodent and chicken N-CAM. On the basis of their chromatographic behavior and substrate specificity, the 2 kinases are glycogen synthase kinase 3 (GSK-3) and casein kinase I (CK I). The 2 kinases phosphorylate N-CAM rapidly, to a high stoichiometry and with a low Km for N-CAM, suggesting that the phosphorylation of N-CAM by these kinases is physiologically relevant. Both enzymes phosphorylate the 2 larger N-CAM polypeptides in vitro in the cytoplasmic domain on threonyl residues that are phosphorylated to a low level in vivo. In addition, the threonyl residues are close to seryl residues phosphorylated to a high level in vivo. Prior phosphorylation at the in vivo sites appears to be a prerequisite for phosphorylation by GSK-3 and CK I. Taken together, the results suggest that N-CAM may be physiologically phosphorylated on 2 sets of interrelated sites, one demonstrable in vivo and one in vitro. Phosphorylation on the "in vivo" sites is resistant to dephosphorylation and may be constitutive, while phosphorylation on the "in vitro" sites is much more labile.
...
PMID:Identification of two protein kinases that phosphorylate the neural cell-adhesion molecule, N-CAM. 254 81

Purified inhibitor of the cyclic AMP-dependent protein kinase (PKI) has been used as a probe to determine if hormone and cyclic AMP-induced activation of the cardiac alkaline triacylglycerol (TG) lipase is mediated through the cAMP-dependent protein kinase. Addition of CAM (cyclic AMP, Mg-ATP, and 3-isobutyl, 1-methylxanthine) to any of the four fractions (homogenate, 10,000 g supernatant, 105,000 g supernatant, or heparin-Sepharose eluate) from heparin perfused heart activated the TG lipase 60% to 110%. Preincubation of these fractions with 33 ng of PKI had no effect on control enzyme activity. Addition of PKI (33 ng) to extracts following CAM activation had little effect on homogenate TG lipase activity, but reduced activities in 10,000 g and 105,000 g supernatant fractions to their respective control levels, and inhibited TG hydrolase activity of activated heparin-Sepharose eluate to 50% below the control activity. If extracts were preincubated with PKI prior to CAM addition, TG lipase activity was reduced to approximately 50% below control levels in all fractions. PKI addition (33 ng) to 105,000 g supernatant obtained from hearts stimulated 60% by epinephrine perfusion reduced activity to 50% below the control level. PKI inhibition of TG lipase activity of 105,000 g supernatant could be reversed by adding 0.5 microgram of catalytic subunit of protein kinase (PKC) to the extract. The inhibition below control levels caused by CAM and PKI indicate that the PKI-PKC complex by itself or in combination with other extract molecules, has an inhibitory effect on the TG lipase.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Protein kinase inhibitor blocks the activation of a myocardial triacylglycerol lipase. 282 94

The phenobarbital-inducible form of cytochrome P-450 purified from rabbit liver microsomes is phosphorylated by cAMP-dependent protein kinase at a single site, the serine residue in position 128 of the amino acid sequence. The serine is located in a characteristic recognition sequence for cAMP-dependent protein kinase and is part of a primary structure which is conserved during evolution, present also in phenobarbital-inducible rat cytochrome and cytochrome P-450 CAM from Pseudomonas putida. The contribution of these findings to our understanding of the structure and membrane topology of cytochrome P-450 LM2 and its turnover regulated by phosphorylation is discussed.
...
PMID:The site of cyclic AMP-dependent protein kinase catalyzed phosphorylation of cytochrome P-450 LM2. 299 Oct 8


1 2 3 4 Next >>

---