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

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Query: EC:2.7.11.17 (CaMKII)
4,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Protein phosphatase 2A (PP2A) isolated from whole rat brain homogenate supernatants has been compared with that extracted from rat synaptosomal membranes. Both purified enzymes are comprised of the three known PP2A polypeptide chains of 65 (A subunit), 55 (B/B' subunit), and 38 (C subunit) kDa and have okadaic acid inhibition curves (Ki = 0.05 nM) nearly identical to that reported for skeletal muscle PP2A. The isolated 38-kDa subunit of rat brain PP2A appears to contain phosphotyrosine based on cross-reactivity with a specific monoclonal antibody (PY-20). Amino acid compositions and sequences of peptides isolated from the 65- and 38-kDa species correspond to regions of the cDNA-deduced sequences of the regulatory and catalytic subunits of protein phosphatase 2A from several sources. Studies reported here also demonstrate that autophosphorylated protein kinases, particularly Ca2+/calmodulin-dependent protein kinase II (CaM kinase II), are excellent substrates for brain PP2A. Furthermore, Ca(2+)-dependent K(+)-depolarization of hippocampal synaptosomes was accompanied by a sequential increase, then decrease, in CaM kinase II phosphorylation level over a 45-s time course. The decrease was blocked by 1 nM okadaic acid. These data demonstrate that the type 2A protein phosphatase is present at the synapses of CNS neurons where its localization could alter the functions of phosphoproteins involved in synaptic plasticity.
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PMID:Rat brain protein phosphatase 2A: an enzyme that may regulate autophosphorylated protein kinases. 779 31

Polyclonal antibody against Ca2+/calmodulin-dependent protein kinase V (CaM kinase V) was prepared from guinea pigs immunized with synthetic polypeptide, based on the partial amino acid sequence of the rat brain enzyme. Immunoblot analysis of purified CaM kinase V revealed two immunoreactive bands with a molecular mass of 41 kDa and minor 40 kDa, respectively. Tissue distribution of CaM kinase V and immunohistochemical localization in rat brain were also investigated. Immunoblotting revealed the presence of immunoreactive proteins with the same molecular mass of 40 and 41 kDa, in the cerebrum, cerebellum, brain stem, pituitary gland, lung, adrenal gland, spleen, liver, colon, heart, stomach, ovary, spinal cord, and thymus. Immunohistochemistry revealed strong staining in the neuronal somata and weak staining in the nuclei. Densely stained regions included the cerebral cortex, the hippocampal formation, the caudatoputamen, the globus pallidus, the hypothalamus, the substantia nigra, the medial geniculate body, the olfactory bulb, the cerebellar cortex and the choroid plexus. CaM kinase V revealed different substrate specificity compared with CaM kinase II. These results lead to the notion that CaM kinase V may exist in 40- and 41-kDa isoforms, is widely distributed in various tissues, and may play an important role in the control of a wide variety of calcium regulated processes in the respective tissues.
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PMID:Ca2+/calmodulin-dependent protein kinase V: tissue distribution and immunohistochemical localization in rat brain. 803 Nov 38

Intact bovine adrenal medullary chromaffin cells were preincubated with 32PO4, and the multiple-site phosphorylation of tyrosine hydroxylase (TH) was studied. Up to eight 32P-labeled peptides were produced by tryptic hydrolysis of TH; however, all of the tryptic phosphopeptides were derived from four phosphorylation sites--Ser8, Ser19, Ser31 and Ser40. In situ regulation of 32P incorporation into the latter three sites was demonstrated with a diverse set of pharmacological agents. 32P incorporation into Ser19 was preferentially increased by brief exposures to depolarizing secretagogues. Longer treatments also increased Ser31 and Ser40 phosphorylation. Nicotine, muscarine and vasoactive intestinal polypeptide--reflecting cholinergic and non-cholinergic components of sympatho-adrenal transmission--each produced different patterns of multiple-site phosphorylation of TH. Nicotine, bradykinin and histamine increased 32P incorporation at each of the three sites whereas muscarine, angiotensin II, endothelin III, prostaglandin E1, GABA and ATP selectively increased Ser31 phosphorylation. Nerve growth factor did not influence TH phosphorylation in chromaffin cells from adult adrenal glands but selectively increased Ser31 phosphorylation in chromaffin cells isolated from calf adrenal glands. 32P incorporation into Ser40 was selectively increased by forskolin and other cAMP-acting agents whereas vasoactive intestinal polypeptide increased Ser31 and Ser40 phosphorylation. Thus, the phosphorylation of TH in bovine chromaffin cells appears to be regulated at three sites by three separate intracellular signaling pathways--Ser19 via Ca2+/calmodulin-dependent protein kinase II; Ser31 via ERK (MAP2 kinases); and Ser40 via cAMP-dependent protein kinase. These signaling pathways, as well as the extracellular signals that were effective in stimulating them, are similar to those previously described for TH in rat pheochromocytoma cells. However, several of the pharmacological agents produced different patterns of multiple-site TH phosphorylation in the bovine chromaffin cells. These differences between tissues could be accounted for by differences in the coupling/access between the extracellular signal transduction systems and the intracellular signaling pathways as opposed to differences in the intracellular signaling pathways per se.
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PMID:Multiple signaling pathways in bovine chromaffin cells regulate tyrosine hydroxylase phosphorylation at Ser19, Ser31, and Ser40. 809 28

The phosphorylation of one receptor that occurs as a result of the stimulation of a different receptor on a cell is a common mechanism for heterologous regulation or "cross-talk," which has been implicated in desensitization. In this work, we focus on the mechanisms of phosphorylation of the rat pancreatic acinar cell cholecystokinin (CCK) receptor that occur upon stimulation of this cell by various agonists. Phosphorylation was allowed to occur in dispersed intact acinar cells in response to the experimental manipulation, and the phosphoreceptor was subsequently purified and quantified as an indication of response. Agonists such as vasoactive intestinal polypeptide and secretin, which act via activation of adenylate cyclase, had no effect on CCK receptor phosphorylation, whereas carbamylcholine and bombesin stimulated increased phosphorylation of the CCK receptor. Because these agents would be expected to activate protein kinase C (PKC) as well as a number of calcium-sensitive kinases and phosphatases, these activities were further dissociated by using more direct activators and inhibitors acting intracellularly. Manipulation of calcium independent of PKC by using a calcium ionophore, inhibition of calcium/calmodulin-dependent kinase II, and inhibition of calcium-dependent protein phosphatase type 2B had no effect on the state of CCK receptor phosphorylation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mechanisms of heterologous agonist-stimulated phosphorylation of cholecystokinin receptor. 817 63

Activation of a calmodulin (CaM)-dependent protein kinase associated with rabbit skeletal-muscle sarcoplasmic reticulum (SR) results in the phosphorylation of polypeptides of 450, 360, 165, 105, 89, 60, 34 and 20 kDa. Radioligand-binding studies indicated that a membrane-bound 60 kDa polypeptide contained both CaM- and ATP-binding domains. Under renaturing conditions on nitrocellulose blots, the 60 kDa polypeptide of the membrane exhibited CaM-dependent autophosphorylation activity, suggesting that it was the CaM-dependent protein kinase of SR. Ca2+/CaM-independent autophosphorylation of polypeptides of 62 and 45 kDa was found to occur in the light SR, whereas the Ca2+/CaM-dependent autophosphorylation activity was enriched in the heavy SR. Both these kinase activities were absent from transverse tubules, although these membranes were enriched in CaM-binding polypeptides of 160, 100 and 80 kDa. In the absence of Ca2+, CaM bound to a 33 kDa polypeptide of the membrane. The purified ryanodine receptor was not phosphorylated by the purified CaM kinase, although it was a substrate for protein kinase C. Affinity-purified antibodies to brain CaM kinase II cross-reacted with the 60 kDa polypeptide in Western blots and immunoprecipitated the 60 kDa polypeptide, along with the 360, 105, 89, 34 and 20 kDa phosphoproteins, from Nonidet-P-40-solubilized SR membranes. Antibodies raised against the 60 kDa kinase polypeptide did not cross-react with the other phosphoproteins, suggesting that these polypeptides were distinct and unrelated. Subcellular distribution of the 60 kDa kinase indicated the specific association of the polypeptide with the junctional-face membrane of SR. The CaM-dependent incorporation of 32P into various membrane proteins was inhibited by the CaM kinase II fragment (290-309), with an IC50 value of 2 nM for the inhibition of incorporation into the 60 kDa kinase polypeptide. Recent studies [Wang and Best (1992) Nature (London) 359, 739-741] have shown that a CaM kinase activity intrinsic to the membrane can inactivate the Ca(2+)-release channel of skeletal muscle SR. Since our results demonstrate that the 60 kDa polypeptide of SR is a CaM-dependent protein kinase, we suggest that this kinase, through its associations, may be responsible for gating the Ca(2+)-release channel.
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PMID:A 60 kDa polypeptide of skeletal-muscle sarcoplasmic reticulum is a calmodulin-dependent protein kinase that associates with and phosphorylates several membrane proteins. 824 Mar 1

We have expressed the rat brain Ca2+/calmodulin (CaM)-dependent protein kinase type IV in insect cells. The recombinant enzyme is produced as a single polypeptide that migrates on SDS-polyacrylamide gel electrophoresis at 61 kDa. Recombinant CaM kinase IV undergoes slow CaM-dependent autophosphorylation. The autophosphorylation of CaM kinase IV occurs on serine residues but is not accompanied by the generation of a CaM-independent activity, as previously reported for the cerebellar enzyme. Comparison of peptide and protein phosphorylation by the recombinant CaM kinase IV and the cerebellar enzyme showed differences in their catalytic activities. The deduced primary sequence of CaM kinase IV contained a domain, 315Phe-Asn-Ala-Arg-Arg-Lys-Leu-Lys323, also found in the regulatory domain of CaM kinase II alpha (residues 293-300). Truncation of CaM kinase IV at Leu313 (at a position analogous to Leu290 in CaM kinase II alpha) generated a fully active, CaM-independent enzyme. This truncated enzyme no longer bound CaM. These data confirm that CaM kinase IV demonstrates intrasteric regulation by an autoinhibitory domain and provides insight into a potentially common mechanism for the regulation of the CaM-dependent multifunctional protein kinases. A number of synthetic peptides were examined for their phosphorylation by both CaM kinase II and IV. These studies showed that several peptides derived from phospholamban were preferential substrates for CaM kinase II whereas a peptide derived from S6 ribosomal protein was selectively phosphorylated by CaM kinase IV. Kinetic analysis of several peptide substrates suggests that while both CaM kinase II and IV recognize the sequence motif represented by R-X-X-T/S, other structural features are also involved in defining the unique substrate specificity of CaM kinase IV.
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PMID:Biochemical characterization of the multifunctional Ca2+/calmodulin-dependent protein kinase type IV expressed in insect cells. 825 36

Four forms of the Drosophila Ca2+/calmodulin-dependent protein kinase II are generated from a single gene by alternative splicing (Ohsako et al. (1993) J. Biol. Chem. 268, 2052-2062). We identified a fifth form of the cDNA encoding the enzyme expressed in the ovary, unfertilized egg and early embryos by reverse transcription-polymerase chain reaction, which suggests that it is maternally derived. The fifth form was also generated from the gene by alternative splicing and was identical to the cDNA encoding the 530-amino-acid polypeptide, the longest of the four forms previously identified, except that it lacked exon 11. Three splicing derivatives which lost one amino acid from the 509- and 530-amino-acid polypeptides were also found in 4 to 10 h embryos.
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PMID:Identification of an alternative form of the Drosophila Ca2+/calmodulin-dependent protein kinase II that is maternally derived. 831 62

A cDNA encoding the beta polypeptide of Ca2+/calmodulin-dependent protein kinase IV (CaM kinase IV) was isolated and sequenced from a rat cerebellar cDNA library. By in situ hybridization histochemistry, we demonstrated the differential gene expression for alpha and beta polypeptides of CaM kinase IV in mature and developing rat brains using oligonucleotide probes specific for each polypeptide.
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PMID:Cloning and sequencing of a gene encoding the beta polypeptide of Ca2+/calmodulin-dependent protein kinase IV and its expression confined to the mature cerebellar granule cells. 841 63

Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) gamma-subunits were cloned from a porcine aortic smooth muscle cDNA library resulting in identification of alternatively spliced CaM kinase II gammaB- and gammaC-subunits and a novel gamma-subunit variant predicted to encode a 60.2-kDa polypeptide, which was designated the gammaG-subunit. A clone predicted to encode a 62. 2-kDa gamma-subunit, designated as gammaE, was isolated with a variable domain structure similar to a gammaB-subunit but with a 114-nucleotide insertion in the conserved "association" domain of CaM kinase II subunits. A full-length gammaE-subunit construct expressed in COS cells resulted in multimeric CaM kinase II holoenzymes (470 kDa) with activation and autoregulatory properties similar to expressed holoenzymes composed of gammaB-, gammaC-, or gammaG-subunits. Expression of gammaE and related gamma-subunit mRNAs containing the 114-base insertion was documented in porcine tissues by reverse transcriptase-polymerase chain reaction. CaM kinase II subunits containing the 38-amino acid insert were identified by Western analysis of partially purified CaM kinase II from carotid arterial smooth muscle and brain using a sequence-specific anti-peptide antibody. Immunoprecipitations of tissue homogenates indicated a comparatively high level of expression of subunits containing the insert in brain and provided evidence for their co-assembly with other more abundant subunits into CaM kinase II heteromultimers. Our analyses indicate the following patterns of gamma-subunit expression: vascular smooth muscle, gammaB > gammaC > gammaE,G; heart, gammaB > gammaE,C > gammaG; brain, gammaE and related subunits >> gammaA,B,C,G.
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PMID:Novel Ca2+/calmodulin-dependent protein kinase II gamma-subunit variants expressed in vascular smooth muscle, brain, and cardiomyocytes. 908 77

Plant genomes encode a variety of protein kinases, and while some are functional homologues of animal and fungal kinases, others have a novel structure. This review focuses on three groups of unusual membrane-associated plant protein kinases: receptor-like protein kinases (RLKs), calcium-dependent protein kinases (CDPKs), and histidine protein kinases. Animal RLKs have a putative extracellular domain, a single transmembrane domain, and a protein kinase domain. In plants, all of the RLKs identified thus far have serine/threonine signature sequences, rather than the tyrosine-specific signature sequences common to animals. Recent genetic experiments reveal that some of these plant kinases function in development and pathogen resistance. The CDPKs of plants and protozoans are composed of a single polypeptide with a protein kinase domain fused to a C-terminal calmodulin-like domain containing four calcium-binding EF hands. No functional plant homologues of protein kinase C or Ca2+/calmodulin-dependent protein kinase have been identified, and no animal or fungal CDPK homologues have been identified. Recently, histidine kinases have been shown to participate in signaling pathways in plants and fungi. ETR1, an Arabidopsis histidine kinase homologue with three transmembrane domains, functions as a receptor for the plant hormone ethylene. G-protein-coupled receptors, which often serve as hormone receptors in animal systems, have not yet been identified in plants.
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PMID:Unusual membrane-associated protein kinases in higher plants. 969 Nov 14


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