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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the presence of and the endogenous substrates for Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) in cultured bovine adrenal medullary cells. By a series of chromatographic steps using DEAE-cellulose, calmodulin affinity, and Sephacryl S-300 columns, we partially purified two CaM kinases (peaks I and III) and one calmodulin-binding protein (peak II). Both of the kinases (peaks I and III) showed broad substrate specificities. Peak I, but not peak III, was immunoprecipitated with an antibody against rat brain CaM kinase II, suggesting that peak I is CaM kinase II or a closely associated CaM kinase. Although the anticaldesmon antibody recognized a 77-kDa protein (low molecular mass caldesmon) in crude preparations from the cells, the protein in peak II was not immunoblotted with the antibody. The peak II protein was phosphorylated by the CaM kinase in peak I but not by the CaM kinase in peak III. Peak I kinase also phosphorylated purified tyrosine hydroxylase and several proteins from chromaffin granule membranes. Stimulation of cultured bovine adrenal medullary cells with 56 mM K+ evoked rapid increases in 45Ca2+ influx and autonomous CaM kinase II activity, both of which were attenuated by the addition of 20 mM MgSO4, an inhibitor of voltage-dependent Ca2+ channels. These results suggest that an isozyme of CaM kinase II exists in adrenal medullary cells and is activated by cell depolarization. Furthermore, the peak II protein is apparently a novel endogenous substrate for CaM kinase II.
Mol Pharmacol 1994 Sep
PMID:Occurrence and activation of Ca2+/calmodulin-dependent protein kinase II and its endogenous substrates in bovine adrenal medullary cells. 793 21

Phosphorylation of the regulatory light chain of myosin by the Ca2+/calmodulin-dependent myosin light chain kinase plays an important role in smooth muscle contraction, nonmuscle cell shape changes, platelet contraction, secretion, and other cellular processes. Smooth muscle myosin light chain kinase is also phosphorylated, and recent results from experiments designed to satisfy the criteria of Krebs and Beavo for establishing the physiological significance of enzyme phosphorylation have provided insights into the cellular regulation and function of this phosphorylation in smooth muscle. The multifunctional Ca2+/calmodulin-dependent protein kinase II phosphorylates myosin light chain kinase at a regulatory site near the calmodulin-binding domain. This phosphorylation increases the concentration of Ca2+/calmodulin required for activation and hence increases the Ca2+ concentrations required for myosin light chain kinase activity in cells. However, the concentration of cytosolic Ca2+ required to effect myosin light chain kinase phosphorylation is greater than that required for myosin light chain phosphorylation. Phosphorylation of myosin light chain kinase is only one of a number of mechanisms used by the cell to down regulate the Ca2+ signal in smooth muscle. Since both smooth and nonmuscle cells express the same form of myosin light chain kinase, this phosphorylation may play a regulatory role in cellular processes that are dependent on myosin light chain phosphorylation.
Mol Cell Biochem 1993 Nov
PMID:Phosphorylation of myosin light chain kinase: a cellular mechanism for Ca2+ desensitization. 793 54

Numerous studies over the past decade have established a role(s) for protein phosphorylation in modulation of synaptic efficiency. This article reviews this data and focuses on putative functions of Ca2+/calmodulin-dependent protein kinase II (CaM-kinase II) which is highly concentrated at these synapses which utilize glutamate as the neurotransmitter. Evidence is presented that CaM-kinase II can phosphorylate these glutamate receptor/ion channels and enhance the ion current flowing through them. This may contribute to mechanisms of synaptic plasticity that are important in cellular paradigms of learning and memory such as long-term potentiation in the hippocampus.
Mol Cell Biochem 1993 Nov
PMID:Calcium/calmodulin-dependent protein kinase II: role in learning and memory. 793 66

Phosphorylation of CREB (cyclic AMP [cAMP]- response element [CRE]-binding protein) by cAMP-dependent protein kinase (PKA) leads to the activation of many promoters containing CREs. In neurons and other cell types, CREB phosphorylation and activation of CRE-containing promoters can occur in response to elevated intracellular Ca2+. In cultured cells that normally lack this Ca2+ responsiveness, we confer Ca(2+)-mediated activation of a CRE-containing promoter by introducing an expression vector for Ca2+/calmodulin-dependent protein kinase type IV (CaMKIV). Activation could also be mediated directly by a constitutively active form of CaMKIV which is Ca2+ independent. The CaMKIV-mediated gene induction requires the activity of CREB/ATF family members but is independent of PKA activity. In contrast, transient expression of either a constitutively active or wild-type Ca2+/calmodulin-dependent protein kinase type II (CaMKII) fails to mediate the transactivation of the same CRE-containing reporter gene. Examination of the subcellular distribution of transiently expressed CaMKIV and CaMKII reveals that only CaMKIV enters the nucleus. Our results demonstrate that CaMKIV, which is expressed in neuronal, reproductive, and lymphoid tissues, may act as a mediator of Ca(2+)-dependent gene induction.
Mol Cell Biol 1994 Sep
PMID:Calcium/calmodulin-dependent protein kinase types II and IV differentially regulate CREB-dependent gene expression. 806 43

The expression of mRNAs encoding gamma and delta subunits of Ca2+/calmodulin-dependent protein kinase type II (CaM kinase II) in the brain of mature and postnatally developing rats was examined by in situ hybridization histochemistry. At the adult stage, mRNAs for both subunits were expressed in the olfactory bulb, and piriform cortex. The cerebral neocortex expressed the gamma subunit mRNA evenly through the layers II to VI at a moderate level, whereas the delta subunit mRNA was expressed in a distinctly laminar distribution. The hippocampal pyramidal and dentate granule cells expressed the gamma subunit mRNA intensely without any significant expression signals for the delta subunit. In the cerebellum, moderate expression signals for the gamma subunit were confined to the Purkinje cell layer, while intense expression signals for the delta subunit were detected in the cerebellar granule cell layer, without any significant expression signals in the Purkinje cell layer. In the spinal cord, mRNA for the gamma subunit was expressed in neurons throughout the gray matter, while the expression of mRNA for the delta subunit was confined to neurons in laminae I and IX. The expression pattern of genes for both subunits was basically accomplished at birth with lower intensity, except for the striatum and cerebellar Purkinje cells, which transiently expressed mRNA for the gamma and delta subunits, respectively, at birth. These results indicate that the expression of genes for each of the subunits of CaM kinase II is differentially regulated in various brain regions and that the individual subunits are involved in differential functions in mature and developing rat brain.
Brain Res Mol Brain Res 1993 Oct
PMID:Differential expression of mRNAs encoding gamma and delta subunits of Ca2+/calmodulin-dependent protein kinase type II (CaM kinase II) in the mature and postnatally developing rat brain. 825 81

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.
Brain Res Mol Brain Res 1993 Aug
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

We have visualized the distribution of autophosphorylated type II CaM kinase in neural tissue with the use of two complementary antibodies: a monoclonal antibody that binds to the alpha and beta subunits of the kinase only when they are autophosphorylated at threonine-286 (287 in beta) and affinity-purified rabbit antibodies that bind to both subunits only when they are not phosphorylated at these residues. We used these antibodies to double-label organotypic hippocampal cultures, detecting the mouse monoclonal antibody with rhodamine and the rabbit polyclonal antibodies with fluorescein. In double-exposed photographs, the ratios of intensities of the two fluorophores revealed the relative proportion of autophosphorylated and nonphosphorylated kinase in individual neurons throughout the cultures. We found that autophosphorylated and nonphosphorylated kinase are colocalized throughout most neurons rather than segregated within distinct cells or subcellular domains. However, the variations in intensity of the two fluorophores indicated that the proportion of autophosphorylated kinase is consistently higher in neuronal somas than in the neuropil. Incubation of the cultures in Ca2+ free medium dramatically reduced both the level of autophosphorylated kinase detected biochemically and the relative intensity of fluorescent staining with the phosphokinase specific monoclonal antibody. These results support the hypothesis that regulation of Ca(2+)-independent CaM kinase activity in vivo occurs by a dynamic equilibrium between autophosphorylation and dephosphorylation and that this equilibrium is maintained, at varying steady-state levels, in all parts of neurons.
Mol Biol Cell 1993 Feb
PMID:Autophosphorylation of type II CaM kinase in hippocampal neurons: localization of phospho- and dephosphokinase with complementary phosphorylation site-specific antibodies. 844 14

The gene for the alpha isoform of Ca2+/calmodulin-dependent kinase II (alpha CaMKII) codes for a multifunctional protein kinase that is found exclusively in the brain. Here we show that in skeletal muscle, an alternative nonkinase product, hereafter referred to as alpha KAP (alpha CaMKII association protein), is expressed from the same gene. alpha KAP consists of a C-terminal region that is identical to the association domain of alpha CaMKII, with the exception of 11 amino acids inserted in the variable region. The N-terminal sequence of alpha KAP is highly hydrophobic and not present in any known CaMKII protein. The catalytic and regulatory domains of alpha CaMKII are missing in alpha KAP. Analysis of the exon-intron structure revealed that the alpha KAP transcript is derived from the alpha CaMKII gene by alternative promoter usage and RNA splicing. The transcriptional start site of alpha KAP mRNA is located within an intron of the alpha CaMKII gene. Therefore, the relationship between alpha KAP and alpha CaMKII is that of a gene within a gene. Immunostaining using anti-alpha KAP antibodies suggests that alpha KAP is associated with sarcomeres of skeletal muscle fibers. On the basis of its primary structure and specific location, the possible function of alpha KAP as an anchoring protein for CaMKII is discussed.
Mol Cell Biol 1996 Jan
PMID:An alternative, nonkinase product of the brain-specifically expressed Ca2+/calmodulin-dependent kinase II alpha isoform gene in skeletal muscle. 852 7

We have recently isolated a new endogenous substrate of 70 kDa for Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) from bovine adrenal medullary cells (Yanagihara, N., Toyohira, Y., Yamamoto, H., Ohta, Y., Tsutsui, M., Miyamoto, E., and Izumi, F. (1994) Mol. Pharmacol. 46, 423-430). Here we report the sequence analysis of the 70-kDa protein and examine its phosphorylation by various protein kinases in vitro and by depolarization of the cultured cells. Protein sequencing and immunoblotting revealed that the 70-kDa protein is chromogranin A (CgA) or a closely related protein. Partially purified CgA was phosphorylated by cyclic AMP-dependent protein kinase and protein kinase C as well as CaM kinase II. Tryptic phosphopeptide mapping patterns of CgA differed among these protein kinases. In 32P-labeled bovine adrenal medullary cells, 56 mM K+ increased the phosphorylation of CgA and catecholamine secretion in similar time- and concentration-dependent manners, both of which were inhibited by 20 mM MgSO4, an inhibitor of voltage-dependent Ca2+ channels. These findings suggest that CgA serves as a substrate for several multifunctional protein kinases and that the elevation of the intracellular Ca2+ stimulates the phosphorylation of CgA associated with catecholamine secretion in cultured adrenal medullary cells.
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PMID:Phosphorylation of chromogranin A and catecholamine secretion stimulated by elevation of intracellular Ca2+ in cultured bovine adrenal medullary cells. 866 39

Phosphorylation of cardiac junctional and free sarcoplasmic reticulum (SR) by protein kinase C (PKC) isoforms alpha and beta was investigated. Both SR and PKC were isolated from canine heart. Junctional and free SR vesicles were prepared by calcium-phosphate-loading. The substrate specificities of PKC alpha and PKC beta were found to be similar in both SR fractions. A high molecular weight junctionally-associated protein was phosphorylated by PKA, PKC and an endogenous Ca2+/calmodulin-dependent protein kinase activity: the highest levels of phosphate incorporation being catalysed by the latter kinase. In addition to this high molecular weight junctionally-associated protein, PKC induced phosphorylation of 45, 96 kDa and several proteins of greater than 200 kDa in junctional SR. A protein of 96 kDa was phosphorylated by both isoforms in junctional and free SR. The major substrate for PKA, PKC alpha, PKC beta and the Ca2+/calmodulin-dependent protein kinase, in both junctional and free SR, was phospholamban. Although the phosphorylation of phospholamban by PKC was activated by Ca2+, a component of this activity appeared to be independent of Ca2+. PKC-mediated phosphorylation of phospholamban was fully activated by 1 microM Ca2+ whereas the Ca2+/calmodulin dependent kinase required concentrations in excess of 5 microM Ca2+. In the in vitro system employed in these studies, the concentrations of either PKC alpha or the catalytic subunit of PKA required to phosphorylate phospholamban were found to be similar. In addition, in the presence of a 15 kDa sarcolemmal-associated protein, which becomes phosphorylated upon activation of PKC in vivo, phosphorylation of phospholamban by PKC was unaffected. These results demonstrate that, although substrates for both subtypes are found in both junctional and free SR, PKC alpha and PKC beta do not show differences in selectivity towards these substrates.
Mol Cell Biochem 1996 Feb 23
PMID:Phosphorylation of cardiac junctional and free sarcoplasmic reticulum by PKC alpha, PKC beta, PKA and the Ca2+/calmodulin-dependent protein kinase. 870 Jan 63


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