Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adrenal glucocorticoid hormones, released in response to stress activation of the hypothalamic-pituitary-adrenal axis (HPA), are powerful regulators of cellular function. Analysis of early (10 min to <3 h) glucocorticoid inhibition of ACTH secretion from anterior pituitary corticotropes is providing insight into potentially generic genomic mechanisms by which glucocorticoids regulate cellular excitability. Early glucocorticoid inhibition is dependent upon activation of intracellular type II glucocorticoid receptors and induction of new proteins, including the calcium-binding protein calmodulin. Glucocorticoids inhibit ACTH secretion stimulated by neuropeptide activation of the cAMP/protein kinase A (PKA) or protein kinase C (PKC) signaling pathways through mechanisms acting at, or beyond, the level of intracellular free calcium mobilization. Increasing evidence also suggests that the efficacy of early glucocorticoid inhibition is selectively modulated by the PKA pathways. The integration of molecular, electrophysiological, imaging and classic neuroendocrine techniques will further expose the molecular basis of early glucocorticoid inhibition.
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PMID:Mechanism(s) of early glucocorticoid inhibition of adrenocorticotropin secretion from anterior pituitary corticotropes. 1840 9

Calmyrin2 (CaMy2, Cib2) is a novel EF-hand calcium-binding protein found recently in skeletal muscles. CaMy2 mRNA was also detected in brain, but nothing is known about CaMy2 protein localization and properties in the brain. We report cloning and characterization of CaMy2 in rat brain: its expression pattern, intracellular localization and biochemical features. CaMy2 binds Ca2+ and exhibits Ca2+/conformational switch. Moreover, CaMy2 undergoes N-myristoylation without Ca2+/myristoyl switch, is membrane-associated and localizes in neurons together with Golgi apparatus and dendrite markers. CaMy2 transcript and protein are present mainly in the hippocampus and cortex. In cultured hippocampal neurons, CaMy2 is induced upon neuronal activation. Most prominent increase in CaMy2 protein (7-fold), and mRNA (2-fold) occurs upon stimulation of NMDA receptor (NMDAR). The induction is blocked by translation inhibitors, specific antagonists of NMDAR, the Ca2+-chelator BAPTA, and inhibitors of ERK1/2 and PKC, kinases transmitting NMDAR-linked Ca2+ signal. Our results show that CaMy2 level is controlled by NMDAR and Ca2+ and suggest CaMy2 role in Ca2+ signaling underlying NMDAR activation.
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PMID:Biochemical characterization and expression analysis of a novel EF-hand Ca2+ binding protein calmyrin2 (Cib2) in brain indicates its function in NMDA receptor mediated Ca2+ signaling. 1943 56

Presynaptic group III metabotropic glutamate receptors (mGluRs) and Ca(2+) channels are the main neuronal activity-dependent regulators of synaptic vesicle release, and they use common molecules in their signaling cascades. Among these, calmodulin (CaM) and the related EF-hand Ca(2+)-binding proteins are of particular importance as sensors of presynaptic Ca(2+), and a multiple of them are indeed utilized in the signaling of Ca(2+) channels. However, despite its conserved structure, CaM is the only known EF-hand Ca(2+)-binding protein for signaling by presynaptic group III mGluRs. Because the mGluRs and Ca(2+) channels reciprocally regulate each other and functionally converge on the regulation of synaptic vesicle release, the mGluRs would be expected to utilize more EF-hand Ca(2+)-binding proteins in their signaling. Here I show that calcium-binding protein 1 (CaBP1) bound to presynaptic group III mGluRs competitively with CaM in a Ca(2+)-dependent manner and that this binding was blocked by protein kinase C (PKC)-mediated phosphorylation of these receptors. As previously shown for CaM, these results indicate the importance of CaBP1 in signal cross talk at presynaptic group III mGluRs, which includes many molecules such as cAMP, Ca(2+), PKC, G protein, and Munc18-1. However, because the functional diversity of EF-hand calcium-binding proteins is extraordinary, as exemplified by the regulation of Ca(2+) channels, CaBP1 would provide a distinct way by which presynaptic group III mGluRs fine-tune synaptic transmission.
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PMID:Ca2+-dependent binding of calcium-binding protein 1 to presynaptic group III metabotropic glutamate receptors and blockage by phosphorylation of the receptors. 2185 31

Regucalcin was discovered in 1978 to be a calcium-binding protein that does not contain the EF-hand motif of the calcium-binding domain [M. Yamaguchi and T. Yamamoto, Chem. Pharm. Bull., 26, 1915-1918, 1978]. The regucalcin gene is localized on the X chromosome and its expression is enhanced through various transcription factors. Regucalcin is known to play a multifunctional role as a suppressor protein of cell signaling in many cell types. Regucalcin is expressed in rat brain neurons and it is decreased in the cerebral cortex and hippocampus of the brain with aging. Neuronal Ca(2+) signaling has been implicated in mechanisms of neuronal plasticity like long-term potentiation, which is likely to play an important role in learning and memory. The disturbance of brain Ca(2+) homeostasis may play a pivotal role in the revelation of brain disease. The intracellular Ca(2+) in brain tissues is increased with aging. Aging enhances the entry of Ca(2+) into brain neuronal cells across the plasma membranes. An increase in the brain microsomal Ca(2+)-ATPase activity of rats with aging resulted in calcium accumulation in the microsomes of the Ca(2+)-sequestrating system that is partly related to the brain toxicity by calcium. Regucalcin had an inhibitory effect on rat brain microsomal Ca(2+)-ATPase activity. The suppressive effect of regucalcin on brain microsomal Ca(2+)-ATPase activity was weakened in aged rats. Regucalcin was found to inhibit brain cytosolic protein kinase C. Brain microsomal Ca(2+)-ATPase activity was enhanced by protein kinase C in aged rats. Regucalcin could also inhibit activity of Ca(2+)/calmodulin-dependent protein kinase, protein phosphatase, and Ca(2+)/calmodulin-dependent nitric oxide synthase, which is linked to Ca(2+) signaling, in the cytosol of rat brain neurons. These inhibitory effects of regucalcin were weakened with aging. Regucalcin may play a pivotal role in the regulation of Ca(2+) signaling which is stimulated through a neurotransmitter in the brain neurons with aging.
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PMID:Role of regucalcin in brain calcium signaling: involvement in aging. 2265 98

The A kinase-anchoring protein AKAP79/150 is a postsynaptic scaffold molecule and a key regulator of signaling events. At the postsynapse it coordinates phosphorylation and dephosphorylation of receptors via anchoring kinases and phosphatases near their substrates. Interactions between AKAP79 and two Ca(2+) -binding proteins caldendrin and calmodulin have been investigated here. Calmodulin is a known interaction partner of AKAP79/150 that has been shown to regulate activity of the kinase PKC in a Ca(2+) -dependent manner. Pull-down experiments and surface plasmon resonance biosensor analyses have been used here to demonstrate that AKAP79 can also interact with caldendrin, a neuronal calcium-binding protein implicated in regulation of Ca(2+) -influx and release. We demonstrate that calmodulin and caldendrin compete for a partially overlapping binding site on AKAP79 and that their binding is differentially dependent on calcium. Therefore, this competition is regulated by calcium levels. Moreover, both proteins have different binding characteristics suggesting that the two proteins might play complementary roles. The postsynaptic enrichment, the complex binding mechanism, and the competition with calmodulin, makes caldendrin an interesting novel player in the signaling toolkit of the AKAP interactome.
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PMID:AKAP79/150 interacts with the neuronal calcium-binding protein caldendrin. 2269 56

Melatonin, the main product synthesized by the pineal gland, modulates several brain functions through different mechanisms, some of them involving the activation or participation of calcium binding intracellular proteins, such as the alpha calcium dependent protein kinase C and calmodulin. Another calcium-binding protein is calretinin, which exerts an essential role for adult hippocampal neurogenesis. Melatonin favors calretinin-positive neurons in the dentate gyrus (DG) of young mice but hippocampal neurogenesis and plasma levels of melatonin decrease during aging. Thus, in this study, we analyzed the impact of exogenous supplementation with melatonin in calretinin-neurons and their distribution along the dorsal-ventral DG in the hippocampus at three different time points (1, 3, or 6 months) after daily treatment with melatonin (8 mg/kg) in male Balb/C mice. We found an increase in the number of calretinin-positive neurons in the DG after treatment (>66%). Although a significant decline in the number of calretinin-neurons was found in both treated (~60.46-69.56%) and untreated mice (~68.81-70.34%) with respect to the youngest mice analyzed, melatonin still maintained higher number of cells in the DG. Also, the distribution of calretinin-neurons along the dorsal-ventral DG significantly showed more cells in the ventral-DG of mice treated with melatonin. Together, the data suggest that melatonin also acts on calretinin in the DG, supporting it as a molecule connecting calcium signaling and neuronal development.
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PMID:Melatonin maintains calcium-binding calretinin-positive neurons in the dentate gyrus during aging of Balb/C mice. 2544 80

Regucalcin is a novel calcium-binding protein which does not contain EF-hand motif as a Ca2+ -binding domain. The organization of the rat regucalcin gene consists of seven exons and six introns. Its mRNA is mainly present in liver but slightly in kidney with a size of 1.8 kb. Hepatic regucalcin mRNA expression is stimulated by various factors including calcium, calcitonin, insulin, and oestrogen in rats. The mRNA is also expressed in hepatoma cells (Morris hepatoma and HepG2). Regucalcin plays a role in the maintenance of cytosolic Ca2+ homeostasis in liver cells. Moreover, regucalcin has an inhibitory effect on Ca2+ /calmodulin-dependent enzyme activation, protein kinase C activation, and many Ca2+ -activated enzymes, indicating a role in the regulation of the Ca2+ -signalling system. Recently, regucalcin has been demonstrated to regulate nuclear function in liver cells. Regucalcin can inhibit Ca2+ -activated nuclear DNA fragmentation in rat isolated liver nuclei. Furthermore, the liver nuclear DNA and RNA syntheses are inhibited by regucalcin. Such an effect of regucalcin is also seen in the nuclei of regenerating rat liver. The regucalcin mRNA level is increased in regenerating liver. These findings suggest that regucalcin plays a regulatory role in the suppression for overexpression of proliferative cells.
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PMID:Role of calcium-binding protein regucalcin in regenerating rat liver. 2897 87

Nonmuscle myosin 2 (NM2) has three paralogs in mammals, NM2A, NM2B, and NM2C, which have both unique and overlapping functions in cell migration, formation of cell-cell adhesions, and cell polarity. Their assembly into homo- and heterotypic bipolar filaments in living cells is primarily regulated by phosphorylation of the N-terminally bound regulatory light chain. Here, we present evidence that the equilibrium between these filaments and single NM2A and NM2B molecules can be controlled via S100 calcium-binding protein interactions and phosphorylation at the C-terminal end of the heavy chains. Furthermore, we show that in addition to S100A4, other members of the S100 family can also mediate disassembly of homotypic NM2A filaments. Importantly, these proteins can selectively remove NM2A molecules from heterotypic filaments. We also found that tail phosphorylation (at Ser-1956 and Ser-1975) of NM2B by casein kinase 2, as well as phosphomimetic substitutions at sites targeted by protein kinase C (PKC) and transient receptor potential cation channel subfamily M member 7 (TRPM7), down-regulates filament assembly in an additive fashion. Tail phosphorylation of NM2A had a comparatively minor effect on filament stability. S100 binding and tail phosphorylation therefore preferentially disassemble NM2A and NM2B, respectively. These two distinct mechanisms are likely to contribute to the temporal and spatial sorting of the two NM2 paralogs within heterotypic filaments. The existence of multiple NM2A-depolymerizing S100 paralogs offers the potential for diverse regulatory inputs modulating NM2A filament disassembly in cells and provides functional redundancy under both physiological and pathological conditions.
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PMID:Multiple S100 protein isoforms and C-terminal phosphorylation contribute to the paralog-selective regulation of nonmuscle myosin 2 filaments. 3008 19


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