Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Actin was localized in the four subacrosomal bulges (Camatini et al., Eur. J. Cell Biol. 45:276-281, 1987), which characterize the sperm head of rabbit spermatozoa (Phillips, J. Ultrastruct. Res. 38:591-604, 1972), and in the postacrosomal region (Welch and O'Rand, Dev. Biol. 109:411-417, 1985; Camatini et al., Eur. J. Cell Biol. 45:276-281, 1987). Specific antibodies and indirect immunogold labelling on testis Lowicryl K4M sections and spermatozoa cryosections were used to study the distribution of calmodulin and a spectrin-like protein. This protein was also present close to the shaping membranes of the head. The results presented suggest a membrane-cytoskeletal role of actin, spectrin, and calmodulin.
Mol Reprod Dev 1991 Jan
PMID:Identification of spectrin and calmodulin in rabbit spermiogenesis and spermatozoa. 199 81

Glucocorticoids induce dramatic biochemical and morphological changes in lymphocytes through an unknown process that requires RNA and protein synthesis. In order to identify genes involved in this response, we previously isolated 11 cDNA clones from the murine WEHI-7TG thymoma cell line that correspond to mRNAs induced by glucocorticoids. We now report the isolation of two new cDNA clones whose gene expression is regulated by glucocorticoids in WEHI-7TG cells. We further characterize the two new cDNA clones, as well as those described previously, by examining the response of each of the corresponding mRNAs to glucocorticoids in murine thymocytes. With the exception of two, all cDNAs correspond to genes that are induced by glucocorticoids in murine thymocytes within 4 h of treatment. We previously identified two of the cDNAs as the mouse VL30 retrovirus-like element and the mouse homolog of chondroitin sulfate proteoglycan core protein. We have now identified four additional cDNA clones that correspond to the genes for calmodulin, mitochondrial phosphate carrier protein, immunoglobulin (Ig)-related glycoprotein (GP-70), and the 70 kilodalton autoantigen for Lupus and Graves diseases. Two other cDNA clones represent previously undescribed genes: one shares a high similarity to known sequences for the family of G-protein-coupled receptors and the other to a human placental-specific protein, PP11. Another cDNA appears to contain sequences for an unknown gene and the remnants of a mouse transposon. ETn. The remaining clones represent new, unidentified genes induced by glucocorticoids in murine thymocytes and in the WEHI-7TG cell line.
Mol Endocrinol 1991 May
PMID:Genes newly identified as regulated by glucocorticoids in murine thymocytes. 207 23

Myoblasts contain a receptor specific for 1,25-dihydroxy-vitamin D3. Morphological data have indicated that the hormone stimulates both myoblast proliferation and fusion. The synthesis of myoblast proteins in response to the sterol was studied during the proliferating stage of the cells. Chick embryo myoblast primary cultures (precultured for 24 h in the presence of low levels of 1,25-dihydroxy-vitamin D3 after isolation) were used. Labelling (2 h) of cells incubated in the absence and presence of 1,25-dihydroxy-vitamin D3 (10(-10) M) for 1-12 h with [14C]leucine and [3H]leucine, respectively, followed by coelectrophoresis of double-labelled proteins on sodium dodecyl sulfate polyacrylamide gels showed that the sterol initially stimulates the synthesis of proteins of 60 kDa (1.2 h), 70 kDa (2.4 h) and 80 kDa (4 h). These changes were transient and between 6 and 12 h a protein of 19 kDa was induced. This protein was identified as calmodulin on the basis of its isoelectric point (pI 4.1), Ca2(+)-dependent electrophoretic mobility, ability to bind 45Ca and to interact with an immobilized phenothiazine in a Ca2(+)-dependent manner, and by means of immunoblotting with a specific anti-calmodulin antibody and 3',5'-cyclic AMP phosphodiesterase activation assays. In agreement with these results, hybridization analysis with a specific cDNA probe showed increased calmodulin mRNA levels in myoblasts treated for 4-12 h with 1,25-dihydroxy-vitamin D3. These changes were paralleled by a stimulation of [3H]thymidine incorporation into DNA suggesting that they may be involved in the mitogenic action of the hormone.
Mol Cell Endocrinol 1990 Dec 03
PMID:Stimulation of calmodulin synthesis in proliferating myoblasts by 1,25-dihydroxy-vitamin D3. 209 May 15

We have previously characterized a calmodulin gene from the organism Drosophila melanogaster. In the higher vertebrates a multi-gene system for encoding calmodulin is present and, in at least one invertebrate species, genes encoding highly related calmodulin isotypes exist. We have therefore searched for additional calmodulin genes within D. melanogaster. Although our searches were sensitive enough to detect a relatively divergent gene encoding a calmodulin family protein, we were unable to detect any additional genes for calmodulin per se. Further studies of the structure and expression of the single calmodulin gene of D. melanogaster have established that the gene contains a tiny additional 5' exon encoding only 50 residues of the 5' leader. Sequencing at the 3' terminus has established that the two transcript size classes derived from the gene are produced as a result of alternative polyadenylation site usage. The relative abundance of the two size classes of mRNAs differs throughout the life cycle, indicating developmental regulation of polyadenylation site usage.
J Mol Biol 1990 Jun 20
PMID:Drosophila melanogaster contains a single calmodulin gene. Further structure and expression studies. 211 85

Inhibition of bovine brain calmodulin-sensitive adenylyl cyclase was examined in a system consisting of the reconstituted purified porcine atrial muscarinic acetylcholine receptor, the purified inhibitory guanine nucleotide-binding protein (Gi), and the partially purified stimulatory guanine nucleotide-binding protein.adenylyl cyclase complex. Under conditions where Gi existed mainly as the Gi.GDP complex, adenylyl cyclase was selectively preactivated with guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S). Addition of carbachol formed the receptor.carbachol complex, which catalyzed the exchange of GDP bound to Gi for GTP gamma S, initiating Gi-mediated inhibition of adenylyl cyclase. Adenylyl cyclase activated by calcium plus calmodulin was more sensitive to inhibition by carbachol than either unstimulated adenylyl cyclase or adenylyl cyclase activated by GTP gamma S or forskolin. Studies using the resolved subunits of Gi showed that the beta gamma subunit could inhibit adenylyl cyclase activated by GTP gamma S or calcium plus calmodulin, as well as the unactivated enzyme. The alpha subunit of Gi inhibited adenylyl cyclase only when adenylyl cyclase was activated by calcium plus calmodulin. Possible explanations for these results are discussed.
Mol Pharmacol 1990 Jun
PMID:Reconstitution of muscarinic receptor-mediated inhibition of adenylyl cyclase. 211 6

W-7 (N-(6-amino-hexyl)-5-chloro-1-naphthalenesulfonamide) (0.1 mM), a calmodulin inhibiting compound, suppressed the reincrease of 86Rb+ efflux from pancreatic islets normally seen in response to lowering the glucose concentration from stimulated to basal value. Ionophore (A23187)-induced increase was completely abolished. W-7 inhibited 45Ca2+ uptake and stimulation of 45Ca2+ efflux in response to glucose (11.1 mM) but did not affect K+ (20 mM)-induced 45Ca2+ uptake. Electrical activity of B-cells at 11.1 mM glucose showed a prolongation in burst length in the presence of 0.1 mM W-7. The data suggest that W-7 affects the opening properties of K+ channels resulting in a delayed repolarisation of the cells possibly through its inhibitory action on Ca2(+)-activated calmodulin.
Mol Cell Endocrinol 1990 May 28
PMID:Effect of W-7 on ionic fluxes and electrical activity of mouse pancreatic islets. 211 29

The calmodulin antagonist W-7 inhibits cleavage of 1-cell mouse embryos in a concentration-dependent manner. This inhibition is likely to be specific for a calmodulin-mediated process, since the less active congener W-5 does not inhibit cleavage when used at concentrations of W-7 that do. Concentrations of W-7 that inhibit cleavage and do not inhibit either the uptake or incorporation of [35S]methionine do inhibit [3H]thymidine incorporation; similar concentrations of W-5 do not inhibit [3H]thymidine incorporation. Consistent with W-7's ability to inhibit cleavage by inhibiting DNA synthesis is that addition of W-7 at later times that correspond with exit from S phase results in cleavage to the 2-cell stage. Although W-7 does inhibit cleavage of 1-cell embryos, it does not inhibit transcriptional activation, which occurs in the 2-cell embryo and is characterized by the synthesis of a group of proteins of Mr = 70,000. Results of these experiments suggest a role for calmodulin in the first cell cycle of the mouse embryo and provide another example in which zygotic gene activation is not dependent on progression through the first cell cycle.
Mol Reprod Dev 1990 Jul
PMID:Regulation of mouse preimplantation development: inhibitory effect of the calmodulin antagonist W-7 on the first cleavage. 211 92

The relationships among 153 EF-hand (calcium-modulated) proteins of known amino acid sequence were determined using the method of maximum parsimony. These proteins can be ordered into 12 distinct subfamilies--calmodulin, troponin C, essential light chain of myosin, regulatory light chain, sarcoplasmic calcium binding protein, calpain, aequorin, Stronglyocentrotus purpuratus ectodermal protein, calbindin 28 kd, parvalbumin, alpha-actinin, and S100/intestinal calcium-binding protein. Eight individual proteins--calcineurin B from Bos, troponin C from Astacus, calcium vector protein from Branchiostoma, caltractin from Chlamydomonas, cell-division-cycle 31 gene product from Saccharomyces, 10-kd calcium-binding protein from Tetrahymena, LPS1 eight-domain protein from Lytechinus, and calcium-binding protein from Streptomyces--are tentatively identified as unique; that is, each may be the sole representative of another subfamily. We present dendrograms showing the relationships among the subfamilies and uniques as well as dendrograms showing relationships within each subfamily. The EF-hand proteins have been characterized from a broad range of organismal sources, and they have an enormous range of function. This is reflected in the complexity of the dendrograms. At this time we urge caution in assigning a simple scheme of gene duplications to account for the evolution of the 600 EF-hand domains of known sequence.
J Mol Evol 1990 Jun
PMID:Evolution of EF-hand calcium-modulated proteins. I. Relationships based on amino acid sequences. 211 31

Various pharmacological effectors were used to investigate the mechanism of arachidonic acid release by N-formyl-methionyl-leucyl-phenylalanine (fMLP) and platelet-activating factor (PAF) in guinea pig alveolar macrophages. The fMLP- and PAF-stimulated arachidonic acid release (i) was mimicked by sodium fluoride and inhibited by Bordetella pertussis toxin, suggesting the participation of a guanine nucleotide-binding protein; ii) was mimicked by A23187 but was insensitive to the calmodulin inhibitor R24571, making the involvement of a calmodulin-dependent pathway unlikely; and (iii) was mimicked by 12-O-tetra-decanoyl phorbol 13 acetate (TPA) and was, like the TPA-stimulated release, markedly decreased when protein kinase C (PKC) had been down-regulated by TPA (65% decrease) or inhibited by sphingosine, a diacylglycerol-competitive PKC inhibitor shown to completely abolish the enzyme activity from alveolar macrophages at 40 microM. Moreover, PAF and fMLP, under conditions where they stimulated arachidonic acid release, promoted an appreciable, albeit transient, translocation of PKC, suggesting a possible involvement of the enzyme in the agonist-stimulated process. However, staurosporine, another PKC inhibitor decreasing PKC activity from alveolar macrophages by 60% at 20 nM, failed to alter fMLP- and PAF-stimulated release. These data lead us to suggest that fMLP- and PAF-stimulated arachidonic acid release is mediated by mechanisms involving either a staurosporine-insensitive PKC isoform or a sphingosine-sensitive coupling between a pertussis toxin-sensitive guanine nucleotide-binding protein and phospholipase A2. Finally, the fMLP- and PAF-stimulated arachidonic acid release was inhibited by cholera toxin and was, like A23187-stimulated release, potentiated by N-[2-(methylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride (H8), an exclusive protein kinase A inhibitor in alveolar macrophages, suggesting a negative regulation by protein kinase A.
Mol Pharmacol 1990 Sep
PMID:Mechanism of N-formyl-methionyl-leucyl-phenylalanine- and platelet-activating factor-induced arachidonic acid release in guinea pig alveolar macrophages: involvement of a GTP-binding protein and role of protein kinase A and protein kinase C. 211 77

Previous studies have demonstrated that the microtubule-associated proteins MAP-2 and tau interact selectively with common binding domains on tubulin defined by the low-homology segments alpha (430-441) and beta (422-434). It has been also indicated that the synthetic peptide VRSKIGSTENLKHQPGGG corresponding to the first tau repetitive sequence represents a tubulin binding domain on tau. The present studies show that the calcium-binding protein calmodulin interacts with a tubulin binding site on tau defined by the second repetitive sequence VTSKCGSLGNIHHKPGGG. It was shown that both tubulin and calmodulin bind to tau peptide-Sepharose affinity column. Binding of calmodulin occurs in the presence of 1 mM Ca 2+ and it can be eluted from the column with 4 mM EGTA. These findings provide new insights into the regulation of microtubule assembly, since Ca2+/calmodulin inhibition of tubulin polymerization into microtubules could be mediated by the direct binding of calmodulin to tau, thus preventing the interaction of this latter protein with tubulin.
Mol Cell Biochem 1990 Sep 03
PMID:Calmodulin binds to a tubulin binding site of the microtubule-associated protein tau. 212 88


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