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

Since various secretory stimuli regulate not only secretion but also protein, RNA, and DNA syntheses in salivary glands, we evaluated the effect of secretory stimuli on the phosphorylation state of CREB (cAMP response element-binding protein). Isoproterenol, forskolin, and CPS-cAMP markedly stimulated the phosphorylation of CREB in parotid acinar cells, and PKA inhibitors H-8 and H-89 dose-dependently inhibited it. In contrast, carbachol (CCH) and A23187 decreased CREB phosphorylation, but CCH did not decrease it in the absence of extracellular Ca2+. Although protein phosphatase inhibitor calyculin A alone markedly increased the phosphorylation, it could not prevent CCH-induced dephosphorylation of CREB. CaM kinase IV, a putative protein kinase for CREB in response to Ca2+ elevation, was undetectable in parotid acinar cells.
Biochem Mol Biol Int 1997 Oct
PMID:Regulation of CREB phosphorylation by cAMP and Ca2+ in parotid acinar cells. 935 75

In this review, we attempt to cover the descriptive, biochemical and molecular biological work that has contributed to our current knowledge about RC3/neurogranin function and its role in dendritic spine development, long-term potentiation, long-term depression, learning, and memory. Based on the data reviewed here, we propose that RC3, GAP-43, and the small cerebellum-enriched peptide, PEP-19, belong to a protein family that we have named the calpacitins. Membership in this family is based on sequence homology and, we believe, a common biochemical function. We propose a model wherein RC3 and GAP-43 regulate calmodulin availability in dendritic spines and axons, respectively, and calmodulin regulates their ability to amplify the mobilization of Ca2+ in response to metabotropic glutamate receptor stimulation. PEP-19 may serve a similar function in the cerebellum, although biochemical characterization of this molecule has lagged behind that of RC3 and GAP-43. We suggest that these molecules release CaM rapidly in response to large influxes of Ca2+ and slowly in response to small increases. This nonlinear response is analogous to the behavior of a capacitor, hence the name calpacitin. Since CaM regulates the ability of RC3 to amplify the effects of metabotropic glutamate receptor agonists, this activity must, necessarily, exhibit nonlinear kinetics as well. The capacitance of the system is regulated by phosphorylation by protein kinase C, which abrogates interactions between calmodulin and RC3 or GAP-43. We further propose that the ratio of phosphorylated to unphosphorylated RC3 determines the sliding LTP/LTD threshold in concept with Ca2+/ calmodulin-dependent kinase II. Finally, we suggest that the close association between RC3 and a subset of mitochondria serves to couple energy production with the synthetic events that accompany dendritic spine development and remodeling.
Mol Neurobiol 1997 Oct
PMID:RC3/neurogranin, a postsynaptic calpacitin for setting the response threshold to calcium influxes. 939 8

The effect of regucalcin on Ca2+/calmodulin-dependent protein kinase activity in the cytosol of rat renal cortex was investigated. Regucalcin is a calcium-binding protein which exists in rat liver and renal cortex. Protein kinase activity in renal cortex cytosol was markedly increased by the addition of CaCl2 (0.5 mM) plus calmodulin (10 microg/ml) in the enzyme reaction mixture . This increase was completely prevented by the addition of trifluoperazine (25 microM), an antagonist of calmodulin. The cytosolic Ca2+/calmodulin-dependent protein kinase activity was clearly inhibited by the addition of regucalcin; an appreciable effect of regucalcin was seen at 0.01 microM. The cytosolic Ca2+/calmodulin-dependent protein kinase activity was fairly increased by increasing concentrations of added Ca2+ (100-1000 microM). This increase was markedly blocked by the presence of regucalcin (0.1 microM). The inhibitory effect of regucalcin on the protein kinase activity was also seen with varying concentrations of calmodulin (2-20 microg/ml). These results demonstrate that regucalcin can regulate Ca2+/calmodulin-dependent protein kinase activity in renal cortex cells.
Mol Cell Biochem 1997 Dec
PMID:Inhibitory effect of regucalcin on Ca2+/calmodulin-dependent protein kinase activity in rat renal cortex cytosol. 945 Jun 68

The synapsins are a family of major neuron-specific synaptic vesicle-associated phosphoproteins which play important roles in synaptic function. In an effort to identify molecular tools which can be used to perturb the activity of the synapsins in in vitro as well as in vivo experiments, we have localized the epitopes of a panel of monoclonal antibodies (mAbs) raised against synapsins I and II and have characterized their ability to interfere with the interactions of the synapsins with protein kinases, actin and Src homology-3 (SH3) domains. The epitopes of the six mAbs were found to be concentrated in the N-terminal region within domains A and B for the synapsin II-reactive mAbs 19.4, 19.11, 19.51 and 19.21, and in two C-terminal clusters in the proline-rich domains D for synapsin I (mAbs 10.22, 19.51, 19.11 and 19.8) and G for synapsin II (mAb 19.8). The synapsin II-specific mAbs 19.4 and 19.21, whose overlapping epitopes are adjacent to phosphorylation site 1, specifically inhibited synapsin II phosphorylation by endogenous or exogenous cAMP-dependent protein kinase. While all the anti-synapsin I mAbs were unable to affect the interactions of synapsin I both with Ca2+/calmodulin-dependent protein kinase II and with actin monomers and filaments, mAbs 19.8 and 19.51 were found to inhibit the binding of Grb2 SH3 domains to the proline-rich C-terminal region of synapsin I.
Brain Res Mol Brain Res 1997 Dec 01
PMID:Anti-synapsin monoclonal antibodies: epitope mapping and inhibitory effects on phosphorylation and Grb2 binding. 945 Jun 72

CD5 acts as a coreceptor on T lymphocytes and plays an important role in T-cell signaling and T-cell-B-cell interactions. Costimulation of T lymphocytes with anti-CD5 antibodies results in an increase of the intracellular Ca2+ levels, and subsequently in the activation of Ca2+/calmodulin-dependent (CaM) kinase type IV. In the present study, we have characterized the initial signaling pathway induced by anti-CD5 costimulation. The activation of phosphatidylinositol (PI) 3-kinase through tyrosine phosphorylation of its p85 subunit is a proximal event in the CD5-signaling pathway and leads to the activation of the lipid kinase activity of the p110 subunit. The PI 3-kinase inhibitors wortmannin and LY294002 inhibit the CD5-induced response as assessed in interleukin-2 (IL-2) secretion experiments. The expression of an inactivated Rac1 mutant (Rac1.N17) in T lymphocytes transfected with an IL-2 promoter-driven reporter construct also abrogates the response to CD5 costimulation, while the expression of a constitutively active Rac1 mutant (Rac1-V12) completely replaces the CD5 costimulatory signal. The Rac1-specific guanine nucleotide exchange factor Vav is heavily phosphorylated on tyrosine residues upon CD5 costimulation, which is a prerequisite for its activation. A role for Vav in the CD5-induced signaling pathway is further supported by the findings that the expression of a dominant negative Vav mutant (Vav-C) completely abolishes the response to CD5 costimulation while the expression of a constitutively active Vav mutant [Vav(delta1-65)] makes the CD5 costimulation signal superfluous. Wortmannin is unable to block the Vav(delta1-65)- or Rac1.V12-induced signals, indicating that both Vav and Rac1 function downstream from PI 3-kinase. Vav and Rac1 both act upstream from the CD5-induced activation of CaM kinase IV, since KN-62, an inhibitor of CaM kinases, and a dominant negative CaM kinase IV mutant block the Vav(delta1-65)-and Rac1.V12-mediated signals. We propose a model for the CD5-induced signaling pathway in which the PI 3-kinase lipid products, together with tyrosine phosphorylation, activate Vav, resulting in the activation of Rac1 by the Vav-mediated exchange of GDP for GTP.
Mol Cell Biol 1998 Mar
PMID:Signaling through CD5 activates a pathway involving phosphatidylinositol 3-kinase, Vav, and Rac1 in human mature T lymphocytes. 948 89

Death-associated protein kinase (DAP kinase) has been recently identified as a novel Ca2+/calmodulin-dependent protein kinase and as a potential mediator of gamma interferon-induced cell death of Hela cells, which has cytological characteristics of the programmed cell death. In order to elucidate its functional roles in the rat brain where the programmed cell death is an essential mechanism in the organization of postmitotic neurons during development, we cloned a rat homologue of the human DAP kinase from the rat embryonic brain cDNA library. The deduced amino acid sequence was highly conserved between the two species (93.6%). By in situ hybridization histochemistry, the expression of DAP kinase mRNA was observed in the mantle and ventricular zones of the entire neuraxis on embryonic day 15. However, the overall expression in the brain decreased markedly after birth and the expression was maintained at substantial levels in several restricted mature neuronal populations, such as olfactory bulb, hippocampal formation and cerebellar Purkinje and granule cells. Its wide expression during development and its maintained expression in the restricted mature neuronal population suggest that DAP kinase might be involved in some neuronal functions beyond simply executing the developmental neuronal cell death.
Brain Res Mol Brain Res 1997 Dec 15
PMID:Molecular cloning and developmental expression of a rat homologue of death-associated protein kinase in the nervous system. 949 46

The solution structure of calcium-bound calmodulin (CaM) complexed with an antagonist, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), has been determined by multidimensional NMR spectroscopy. The structure consists of one molecule of W-7 binding to each of the two domains of CaM. In each domain, the W-7 chloronaphthalene ring interacts with four methionine methyl groups and other aliphatic or aromatic side-chains in a deep hydrophobic pocket, the site responsible for CaM binding to CaM-dependent enzymes such as myosin light chain kinases (MLCKs) and CaM kinase II. This competitive binding at the same site between W-7 and CaM-dependent enzymes suggests the mechanism by which W-7 inhibits CaM to activate the enzymes. The orientation of the W-7 naphthalene ring in the N-terminal pocket is rotated approximately 40 degrees with respect to that in the C-terminal pocket. The W-7 ring orientation differs significantly from the Trp800 indole ring of smooth muscle MLCK bound to the C-terminal pocket and the phenothiazine ring of trifluoperazine bound to the N or C-terminal pocket. These comparative structural analyses demonstrate that the two hydrophobic pockets of CaM can accommodate a variety of bulky aromatic rings, which provides a plausible structural basis for the diversity in CaM-mediated molecular recognition.
J Mol Biol 1998 Feb 13
PMID:Solution structure of calmodulin-W-7 complex: the basis of diversity in molecular recognition. 951 29

The expression of calcium-binding protein regucalcin mRNA in the kidney cortex of rats ingested with saline was investigated. The alteration in regucalcin mRNA levels was analyzed by Northern blotting using liver regucalcin complementary DNA (0.9 kb of open reading frame). Rats were freely given saline as drinking water for 7 days. Regucalcin mRNA levels in the kidney cortex were suppressed by saline ingestion. When calcium chloride (10 mg Ca/100 g body weight) was intraperitoneally administered to rats ingested with saline for 7 days, the effect of calcium administration to increase regucalcin mRNA levels was weakened by saline ingestion. Such effect was also seen by the administration of 2.5 and 5 mg Ca/100 g. Regucalcin mRNA levels in the kidney cortex of spontaneous hypertensive rats (SHR) were not appreciably increased by the administration of calcium (10 mg/100 g). Meanwhile, calcium content in the kidney cortex was significantly elevated by the administration of calcium (10 mg/100 g) to normal rats. This increase was weakened in saline-ingested rats. Moreover, Ca2+/calmodulin-dependent protein kinase activity in the cytosol of kidney cortex was significantly decreased by saline ingestion. These results suggest the possibility that saline ingestion-induced suppression of regucalcin mRNA expression in the kidney cortex is partly involved in the attenuation of Ca2+ signalling.
Mol Cell Biochem 1998 Jan
PMID:Stimulatory effect of calcium administration on regucalcin mRNA expression is attenuated in the kidney cortex of rats ingested with saline. 954 10

Ca2+/calmodulin-dependent protein kinase (CaM kinase) I and IV are thought to be activated by CaM kinase kinases (CaMKK). We examined the distribution of mRNAs for two isoforms (alpha and beta) of CaMKKs in the brain by in situ hybridization histochemistry. In the adult rat brain, CaMKK alpha mRNAs are widely distributed throughout the brain, whereas CaMKK beta mRNAs are restricted to some neuronal populations, particularly the cerebellar granule cells.
Brain Res Mol Brain Res 1998 Mar 01
PMID:Localization of the mRNAs for two isoforms of Ca2+/calmodulin-dependent protein kinase kinases in the adult rat brain. 955 71

Diisopropyl phosphorofluoridate (DFP) produces delayed neurotoxicity, known as organophosphorus ester-induced delayed neurotoxicity (OPIDN), in hen, human, and other sensitive species. A single dose of DFP (1.7 mg/kg, se.) produces first mild ataxia followed by paralysis in 7-14 days in hens. DFP treatment also increases in vitro autophosphorylation of Ca2+ calmodulin-dependent protein kinase II (CaM kinase II) and the phosphorylation of several cytoskeletal proteins in the hen brain. To investigate whether increase in CaM kinase II activity is associated with increased expression of its mRNA, we cloned and sequenced CaM kinase II alpha subunit cDNA, and used it to study CaM kinase II expression in brain regions and spinal cord. Hen CaM kinase II alpha subunit differs in 7 amino acids from that of rat CaM kinase II. Its mRNA occurs predominantly as a 6.7 kb message, which is very close to that of human CaM kinase II alpha subunit. Northern blot analysis showed a transient increase in CaM kinase II alpha subunit mRNA in the cerebellum and spinal cord of DFP-treated chickens. The increase in CaM kinase II mRNA expression is consistent with the previously reported increase in its activity in brain and spinal cord, and its increased expression only in cerebellum and spinal cord, which are sensitive to the Wallerian-type degeneration characteristic of OPIDN, suggests the probable role of this enzyme in delayed neurotoxicity.
Mol Cell Biochem 1998 Apr
PMID:cDNA cloning and sequencing of Ca2+/calmodulin-dependent protein kinase IIalpha subunit and its mRNA expression in diisopropyl phosphorofluoridate (DFP)-treated hen central nervous system. 956 39


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