Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
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During third-instar larval development of Drosophila melanogaster, the fat body tissue synthesizes six major methionine-containing polypeptides, three of which are the alpha, beta, and gamma subunits of the hexameric larval serum protein LSP-1, a fourth is the single subunit of the hexameric larval serum protein LSP-2, and the other two are polypeptides P6 and P1. Genomic DNA clones of the six structural genes for the polypeptides were isolated and characterized. Each gene maps by in situ hybridization at a single chromosomal site and appears to be present as a single copy in the genome. The LSP-1 and LSP-2 genes show striking regulatory similarities: The LSP-1 beta and gamma transcripts are first detected in fat bodies within an hour after the second molt, and the LSP-1 alpha and LSP-2 transcripts a few hours later; the four transcripts are subsequently maintained at high levels during most of the third instar and rapidly decrease shortly before pupariation. Ecdysterone increases the levels of at least three of the four LSP transcripts in the fat bodies when ecdysterone-deficient larvae from the temperature-sensitive mutant ecd1 are supplemented with the hormone. The regulatory characteristics of the P6 and P1 genes differ in several ways from those of the LSP genes. Expression of the P6 and P1 genes begins later than the LSP genes, and the levels of the transcripts remain high at the end of the third instar after the LSP transcripts have markedly decreased. Ecdysterone increases the level of the P1 transcript, but not of the P6 transcript, in ecdysterone-deficient ecd1 larvae.
J Mol Appl Genet 1982
PMID:Developmentally regulated gene expression in Drosophila larval fat bodies. 681 15

In spite of the generally well-coordinated synthesis of RNA polymerase core enzyme subunits (alpha, beta and beta') in Escherichia coli, a situation was found during the growth transition from exponential to stationary phase in which this coordination was broken (the order of differential repression being alpha leads to beta' leads to beta; Kawakami et al. (1979). The present study indicates that, during a certain period of the growth transition, twice as much beta subunit is synthesized as beta' subunit and the overproduced beta subunit accumulates as the assembly intermediate alpha 2 beta complex, which is rapidly and preferentially degraded. Two independent factors, i.e., carbon source down-shift and oxygen depletion, were examined separately for their influence on the coordinated regulation of the synthesis of RNA polymerase subunits. The depletion of glucose added as a sole carbon source was accompanied by repression of the synthesis of all core enzyme subunits, while under the same conditions the differential rate of sigma subunit synthesis increased. In contrast, the sudden ending of the oxygen supply resulted in specific repression of the synthesis of only beta and beta' subunits but not of sigma and alpha subunits. The latter result may be explained by the autogenous repression of the rpoBC genes by a temporal increase in the amount of unused cytoplasmic RNA polymerase.
Mol Gen Genet 1982
PMID:Biosynthesis of RNA polymerase in Escherichia coli. XII. Noncoordinate synthesis of core enzyme subunits after suppression of cell growth. 704 23

We report the observation of deuterium Fourier transform NMR spectra (obtained by the quadrupole echo method at 8.5 Tesla, corresponding to a 2H resonance frequency of 55.3 MHz) of [meso-alpha, beta, gamma, delta-2H4], [methyl-1,3-2H6], and [methylene-6,7-b-2H4]heme-labeled aquoferrimyoglobin microcrystals (in approximately 90% saturated (NH4)2SO4 at pH 6.8) from Physeter catodon, using the method of magnetic ordering (Rothgeb, T. M. and Oldfield, E. (1981) J. Biol. Chem. 256, 1432-1446). The results, together with those obtained on suitable diamagnetic derivatives, permit partial determination of the static organization of the heme, and the results obtained are in good agreement with those obtained using x-ray crystallography (Takano, T. (1977( J. Mol. Biol. 110, 537-568). We show that resonances near the paramagnetic iron center are subject to extremely large (approximately 500 ppm) hyperfine shifts, which distort the otherwise symmetric 2H spectra. Temperature dependence studies are required to analyze these shifts, which are an order of magnitude larger than those seen in solution NMR spectroscopy. The overall results suggest that 2H solid state NMR spectroscopy of magnetically ordered paramagnetic protein microcrystals may be a useful method for determination of heme organization in systems that for one reason or another are unsuitable for analysis using x-ray diffraction methods.
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PMID:Nuclear magnetic resonance of hemeprotein crystals. Structure of the heme in Physeter catodon ferrimyoglobin and an analysis of hyperfine shifts. 706 74

Translocation of protein kinase C (PKC) from the cytosol to the plasma membranes is believed to reflect activation of the enzyme. We have studied translocation of PKC in lactotroph-enriched anterior pituitary cell cultures by measuring the incorporation of gamma-32P from [gamma-32P]ATP into a synthetic peptide substrate, MBP4-14, and by immunoblotting of PKC isozymes. Using cells permeabilized with digitonin the effects of PKC cofactors on the distribution of the enzyme were studied. Ca2+ (50 nM) and dioctanoyl-sn-glycerol had no effect when tested alone, but in combination they caused a redistribution of PKC from the soluble to the particulate fraction. Arachidonic acid needed Ca2+ to induce translocation of PKC, while being ineffective under Ca(2+)-free conditions. Western blot analysis of partly purified PKC from lactotroph-enriched pituitary cells revealed the presence of the alpha, beta, delta and zeta isozymes. 12-O-Tetradecanoylphorbol 13-acetate (TPA) and substance P displayed different patterns of redistribution of PKC isozyme immunoreactivity from soluble to membrane-attached forms. Thus, TPA induced time- and dose-dependent (mean effective concentration (EC50) = 1 nM) translocation of the alpha, beta and delta species, while substance P stimulated time- and dose-dependent (EC50 = 1 nM) redistribution of the alpha and beta isozymes. zeta subtype immunoreactivity could not be translocated by either agonist; neither could the immunoreactivity of zeta be down-regulated by long-term treatment (24 h) with TPA. The results indicate that simultaneous activation of phospholipases C and A2 induces a synergistic activation of PKC. Finally it is suggested that substance P may exert some of its effects in lactotrophs by translocation of PKC isozymes alpha and beta.
J Mol Endocrinol 1994 Jun
PMID:Translocation of protein kinase C isozymes in lactotroph-enriched rat anterior pituitary cell cultures: differential effects of substance P and phorbol ester. 752 60

In the central nervous system (CNS), the expression of protein kinase C (PKC) genes is strictly controlled by the developmental stage. We have examined the expression of PKC genes (cPKC alpha, beta, gamma, and nPKC delta, epsilon) in the process of the postnatal development in normal (+/+) C57BL/6 and microphthalmic (mi/mi) C57BL/6 mouse brains by Northern blotting and in situ hybridization. By Northern blotting, the expression level of cPKC gamma mRNA in mi/mi mice was significantly lower than that in +/+ littermates at d 9, 13, and 17. By in situ hybridization analysis, cPKC gamma mRNA-positive cells were detected in hippocampal and Purkinje cells in +/+ and mi/mi mice, but the magnitude of the signals in mi/mi mice was lower than that of +/+ mice, and the number of positive cells was smaller, whereas other isozymes (cPKC alpha, beta, and nPKC delta, epsilon) showed no significant difference between normal and mi/mi mice. The neuronal morphometric analysis by anti-P400 antibody revealed the same number and expression level of P400 protein in cerebellar Purkinje cells compared with +/+ mice. These results indicate that the deficiency of mi gene product causes the delayed expression of the cPKC gamma gene.
J Mol Neurosci 1993
PMID:PKC gamma gene expression is delayed in postnatal central nervous system of mi/mi mice. 752 3

Retinoic acid (RA) is known to have potent effects on development and differentiation. alpha-Fetoprotein (AFP), an oncodevelopmental protein, is transcriptionally activated by RA in several cell lines, but little is known about the mechanism of RA regulation of AFP gene expression. In the present study, we have identified a RA response element (RARE) in the 5'-flanking region of the AFP gene. Using deletion mapping, the RARE was located between -6337 to -6266 of the rat AFP 5'-flanking region, which confers RA responsiveness in a heterologous promoter. Further sequence analysis of this cis-acting element demonstrated a RARE direct repeat sequence of AGGTCA and RARE-like motifs at -6327 and -6319, respectively. This far upstream RARE (AFP-RARE1) can specifically bind to both RAR and RXR proteins in gel mobility shift assays. In co-transfections with RAR alpha, beta, gamma and RXR alpha expression vectors, a reporter gene construct consisting of the AFP-RARE1 sequence ligated upstream of the chloramphenicol acetyltransferase (CAT) gene showed strong RA responsiveness to RAR alpha and RXR alpha with 15- and 25-fold increases in CAT activity, respectively. Furthermore, responsiveness of AFP-RARE1 to RA was independent of orientation. These studies present a novel target for RA action by identifying a RARE in the AFP gene.
Mol Cell Endocrinol 1994 Jul
PMID:Identification of a retinoic acid response element upstream of the rat alpha-fetoprotein gene. 752 84

The characteristics of PKC activation induced by a number of compounds were investigated using PKCs, partially-purified from sources with a naturally high abundance of certain Ca2+ dependent PKC isoforms. Native isoforms were used rather than PKC isoforms expressed from a baculovirus system to assess the effect of tissue specific factors on activity. However, some data using recombinant PKC alpha were included for comparison. The presence of specific PKC isoforms in different tissues was determined using Western blot analysis. Protein kinase C alpha, beta 1, delta, epsilon, and zeta/iota were all present in rat midbrain cytosolic extract, PKC alpha, beta 1, delta, and zeta/iota were present in spleen cytosol, and PKC alpha and zeta/iota were present in COS 7 cell cytosol. The predominance of alpha and beta activities in COS 7 and spleen extracts respectively was confirmed by enzymic assay. The PKC activity assay was configured such that the Ca2+ dependence of the PKC activity induced by different PKC activators could be determined. Phorbol 12,13-dibutyrate (PDBu) was virtually equipotent on the Ca(2+)-dependent PKC activity from midbrain and spleen and slightly less potent on that from COS 7 cells. In the absence of Ca2+, PDBu was considerably less potent overall (as, indeed, were the other PKC activators) and was less potent on COS 7 cell PKC than on those from midbrain or spleen. Mezerein was more potent than PDBu at inducing PKC activity in COS 7 cell extracts in either the absence or presence of Ca2+ whereas in the presence of Ca2+, mezerein was slightly less potent on midbrain and spleen than PDBu and equipotent in the absence of Ca2+. Maximum values for Ca(2+)-independent activation by mezerein indicated that this activator was particularly effective in recruiting Ca(2+)-dependent PKC isoform activity in a Ca2+ free environment. The greater potency of mezerein on PKC alpha was confirmed using PKC alpha and beta further purified from rat spleen by hydroxylapatite (HAP) chromatography. The effects of both PDBu and mezerein were investigated using anterior pituitary tissue where a particularly high potency of mezerein in the absence of Ca2+ was noted. The diacylglycerol, 1,2-dioctanoyl-sn-glycerol (DOG), appeared to cause little or no activation of native Ca(2+)-dependent isoforms in Ca2+ free conditions unlike another longer chain diacylglycerol, 1,2-dioleoyl-sn-glycerol. Also DOG activated midbrain PKCs more potently than PKCs from spleen or COS 7 cells (or lung and pituitary tissue) in the presence of Ca2+.(ABSTRACT TRUNCATED AT 400 WORDS)
Mol Cell Biochem 1995 May 24
PMID:Phorbol ester and diacylglycerol activation of native protein kinase C species from various tissues. 756 42

Retinoid X receptors (RXRs), along with retinoic acid (RA) receptors (RARs), mediate the effects of RA on gene expression. Three subtypes of RXRs (alpha, beta, and gamma) which bind to and are activated by the 9-cis stereoisomer of RA have been characterized. They activate gene transcription by binding to specific sites on DNA as homodimers or as heterodimers with RARs and other related nuclear receptors, including the vitamin D receptor, thyroid hormone receptors (TRs), and peroxisome proliferator-activated receptors. Two additional RXR subtypes (delta and epsilon) isolated from zebra fish cDNA libraries are described here; although both subtypes form DNA-binding heterodimers with RARs and TR, neither binds 9-cis RA, and both are transcriptionally inactive on RXR response elements. In cotransfection studies with TR, the delta subtype was found to function in a dominant negative manner, while the epsilon subtype had a slight stimulatory effect on thyroid hormone (T3)-dependent transcriptional activity. The discovery of these two novel receptors in zebra fish expands the functional repertoire of RXRs to include ligand-independent and dominant negative modulation of type II receptor function.
Mol Cell Biol 1995 Oct
PMID:New retinoid X receptor subtypes in zebra fish (Danio rerio) differentially modulate transcription and do not bind 9-cis retinoic acid. 756 71

Cellular differentiation and proliferation are dependent upon phosphorylation by endogenous protein kinase C (PKC) isozymes in many cell types. Western blotting with a C-terminally directed rabbit polyclonal anti-PKC zeta antibody detected a doublet of approximately 81 kDa in normal hamster pancreatic tissue and hamster pancreatic carcinoma (PC-1) and human pancreatic carcinoma (PANC-1) cells. Preabsorption of the antibody with the specific peptide blocked the appearance of the 81-kDa band, indicating that the band was specifically recognized by the PKC zeta antibody. In contrast, antibodies for PKC alpha, beta, gamma, delta, and epsilon failed to show specific immunoreactivity for normal pancreatic tissue or PANC-1 or PC-1 cells. Immunocytochemical analysis identified PKC zeta in the cytoplasm of ductules and large ducts, to a lesser extent in the islets of the hamster pancreas, and in the normal cultured pancreatic duct epithelial cells and pancreatic carcinoma (PANC-1 and PC-1) cell lines. Specific reactivity was seen by electron microscopy in the ductal cells of the normal pancreatic tissue. In normal pancreatic ductal tissue and primary pancreatic ductal hyperplasia and carcinoma, the proportional labeling of PKC zeta in nuclei and cytoplasm was similar. Our results demonstrating the presence of PKC zeta isozyme in the normal pancreas, cultured normal pancreatic duct epithelial cells, and pancreatic carcinoma cells or carcinoma tissue suggests a role for this isozyme in the normal physiology of the pancreas and perhaps in pancreatic carcinoma.
Mol Carcinog 1995 Nov
PMID:Identification of protein kinase C zeta isozyme in hamster pancreas and pancreatic carcinoma cell lines. 757 13

A protein is usually classified into one of the following five structural classes: alpha, beta, alpha + beta, alpha/beta, and zeta (irregular). The structural class of a protein is correlated with its amino acid composition. However, given the amino acid composition of a protein, how may one predict its structural class? Various efforts have been made in addressing this problem. This review addresses the progress in this field, with the focus on the state of the art, which is featured by a novel prediction algorithm and a recently developed database. The novel algorithm is characterized by a covariance matrix that takes into account the coupling effect among different amino acid components of a protein. The new database was established based on the requirement that the classes should have (1) as many nonhomologous structures as possible, (2) good quality structure, and (3) typical or distinguishable features for each of the structural classes concerned. The very high success rate for both the training-set proteins and the testing-set proteins, which has been further validated by a simulated analysis and a jackknife analysis, indicates that it is possible to predict the structural class of a protein according to its amino acid composition if an ideal and complete database can be established. It also suggests that the overall fold of a protein is basically determined by its amino acid composition.
Crit Rev Biochem Mol Biol 1995
PMID:Prediction of protein structural classes. 758 80


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