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

The soft, starchy endosperm of the maize (Zea mays L.) floury 2 mutant is associated with a reduction in zein mRNA and protein synthesis, unique protein body morphology, and enhanced levels of a 70 kDa protein, that has been shown to be the maize homolog of a chaperonin found in the endoplasmic reticulum. We found an unusual alpha-zein protein of 24 kDa to be consistently associated with the zein fraction from floury 2 mutants. Three additional alpha-zein proteins with molecular weights ranging from ca. 25 to 27 kDa are detected in the storage protein fraction of a high percentage of floury 2 kernels and a low percentage of normal kernels in a genetically segregating population. The four proteins in a genetically segregating population. The four proteins can be distinguished from one another by immunostaining on Western blots. Synthesis of the 24 kDa protein is regulated by Opaque2, since the 24 kDa protein is lacking in the storage protein fraction of opaque2/floury2 double mutants. The synthesis of an abnormal alpha-zein protein in floury2 could explain many features of the mutant, such as the abnormal protein body morphology, induction of the 70 kDa chaperonin, and hypostasis to opaque2 (o2). Although we cannot prove that the accumulation of this protein is responsible for the floury2 phenotype, we were able to detect a restriction fragment length polymorphism (RFLP) linked to the floury2 locus with a 22 kDa alpha-zein probe. We hypothesize that the unique characteristics of the floury2 mutant could be a response to the accumulation of a defective alpha-zein protein which impairs secretory protein synthesis.
Mol Gen Genet 1994 Dec 01
PMID:Synthesis of an unusual alpha-zein protein is correlated with the phenotypic effects of the floury2 mutation in maize. 780 5

Transfected Madin Darby canine kidney (MDCK) cells (3A) expressing human growth hormone (hGH) contain twice as many Golgi stacks as untransfected cells. How MDCK cells, lacking a regulated pathway, deal with (over)expression of a protein hormone, or any exogenous protein, has not been examined in detail. Since hGH constituted 10% of total secreted proteins, it was not apparent why Golgi amplification was needed, unless some enters a nonsecretory compartment. Studies were undertaken to determine hGH fate. By using an inhibitor of protein synthesis, or by analyzing pulse labeled immunoprecipitated hGH, 20-30% of hGH was shown to remain intracellular even after 4 h. That portion might be localized in the endosome/lysosome compartment, because it is post-Golgi. Immunoelectron microscopy with antibodies against hGH, clathrin, and cathepsin D demonstrated clathrin and hGH colocalized, as did hGH and cathepsin D. The latter were found in large vesicles, but no hGH appeared in lysosomes, due to its degradation. Analysis of isolated lysosome/endosomes revealed vesicles containing both hGH and cathepsin D, but more containing only cathepsin D. Endocytosis studies suggested the 3A basolateral endosomal compartment may be more capacious than normal. Thus, 3A Golgi amplification resulted in an expanded endosome compartment to accommodate secretory protein (over)expression.
Cell Mol Biol Res 1993
PMID:Routing of a secretory protein to the endocytic compartment in transfected Madin Darby canine kidney cells. 795 16

Signal recognition particle (SRP) is a cytoplasmic ribonucleoprotein required for targeting a subset of presecretory proteins to the endoplasmic reticulum (ER) membrane. Here we report the results of a series of experiments to define the function of the Schizosaccharomyces pombe homolog of the 54-kDa subunit of mammalian SRP. One-step gene disruption reveals that the Srp54 protein, like SRP RNA, is essential for viability in S. pombe. Precursor to the secretory protein acid phosphatase accumulates in cells in which Srp54 synthesis has been repressed under the control of a regulated promoter, indicating that S. pombe SRP functions in protein targeting. In common with other Srp54 homologs, the S. pombe protein has a modular structure consisting of an amino-terminal G (GTPase) domain and a carboxyl-terminal M (methionine-rich) domain. We have analyzed the effects of 17 site-specific mutations designed to alter the function of each of the four GTPase consensus motifs individually. Several alleles, including some with relatively conservative amino acid substitutions, confer lethal or conditional phenotypes, indicating that GTP binding and hydrolysis are critical to the in vivo role of the protein. Two mutations (R to L at position 194 [R194L] and R194H) which were designed, by analogy to oncogenic mutations in rats, to dramatically decrease the catalytic rate and one (T248N) predicted to alter nucleotide binding specificity produce proteins that are unable to support growth at 18 degrees C. Consistent with its design, the R194L mutant hydrolyzes GTP at a reduced rate relative to wild-type Srp54 in enzymatic assays on immunoprecipitated proteins. In strains that also contain wild-type srp54, this mutant protein, as well as others designed to be locked in a GTP-bound conformation, exhibits temperature-dependent dominant inhibitory effects on growth, while a mutant predicted to be GDP locked does not interfere with the function of the wild-type protein. These results form the basis of a simple model for the role of GTP hydrolysis by Srp54 during the SRP cycle.
Mol Cell Biol 1994 Dec
PMID:The Srp54 GTPase is essential for protein export in the fission yeast Schizosaccharomyces pombe. 796 24

The salivary gland secretion in the dipteran Chironomus tentans is composed of approximately 15 different secretory proteins. The most well known of the corresponding genes are the four closely related Balbiani ring (BR) genes, in which the main part of each approximately 40-kb gene is composed of tandemly arranged repetitive units. Six of the seven additional secretory protein genes described share structural similarities with the BR genes and are members of the same BR multigene family. Here we report the identification of a new secretory protein gene, the sp12 gene, encoding the smallest component of the C. tentans salivary gland secretion. The gene has a corresponding mRNA length of approximately 0.7 kb and codes for a protein with a calculated molecular weight of 7,619 Da. The sp12 gene was characterized in seven Chironomus species. Based on a comparison of the orthologous gene sequences, we conclude that the sp12 gene has a repetitive structure consisting of diverged 21-bp-long repeats. The repeat structure and the codon composition are similar to the so-called SR regions of the BR genes and the sp12 gene may represent a diverged member of the BR multigene family.
J Mol Evol 1994 May
PMID:Structure of the smallest salivary-gland secretory protein gene in Chironomus tentans. 802 27

Expression of a transgene containing 2.25 kb of the 5' flanking region of the rat Clara cell secretory protein gene and the human growth hormone gene was examined in developing mice. Despite an absolute preservation of tissue specificity based on RNA blot analysis, transgene-specific transcripts were detectable as early as 12.5 days of gestation, at least 4 days prior to endogenous Clara cell secretory protein gene expression. As differentiation proceeded, in situ hybridization revealed an increasingly restricted pattern of transgene expression in the developing pulmonary epithelium, such that by day 16.5 of gestation endogenous and transgene expression were confined to identical cells within the bronchiolar epithelium. The temporal discordance in transgene expression suggests the presence of unique cis-acting elements within the Clara cell secretory protein gene, not present in the transgene, which transduce developmental timing within pulmonary epithelium by actively repressing Clara cell secretory protein gene expression during early development. The unique expression of this transgene serves as a lineage marker in the respiratory epithelium and unmasks a temporal and spatial pattern of gene expression not observed in any pulmonary genes.
Am J Respir Cell Mol Biol 1994 Aug
PMID:5' flanking region of the Clara cell secretory protein gene specifies a unique temporal and spatial pattern of gene expression in the developing pulmonary epithelium. 804 73

We used the lung epithelial cell-specific surfactant protein B (SPB) gene promoter as a model with which to investigate mechanisms involved in transcriptional control of lung-specific genes. In a previous study, we showed that the SPB promoter specifically activated expression of a linked reporter gene in the continuous H441 lung cell line and that H441 nuclear proteins specifically protected a region of this promoter from bp -111 to -73. In this study, we further show that this region is a complex binding site for thyroid transcription factor 1 (TTF-1) and hepatocyte nuclear factor 3 (HNF-3). Whereas TTF-1 bound two highly degenerate and closely spaced sites, HNF-3 proteins bound a TGT3 motif (TGTTTGT) that is also found in several liver-specific gene regulatory regions, where it appears to be a weak affinity site for HNF-3. Point mutations of these binding sites eliminated factor binding and resulted in significant decreases in transfected SPB promoter activity. In addition, we developed a cotransfection assay and showed that a family of lung-specific gene promoters that included the SPB, SPC, SPA, and Clara cell secretory protein (CCSP) gene promoters were specifically activated by cotransfected TTF-1. We conclude that TTF-1 and HNF-3 are major activators of lung-specific genes and propose that these factors are involved in a general mechanism of lung-specific gene transcription. Importantly, these data also show that common factors are involved in organ-specific gene expression along the mammalian foregut axis.
Mol Cell Biol 1994 Sep
PMID:The lung-specific surfactant protein B gene promoter is a target for thyroid transcription factor 1 and hepatocyte nuclear factor 3, indicating common factors for organ-specific gene expression along the foregut axis. 806 4

Region I of the Clara cell secretory protein (CCSP; also called CC10) promoter contains at least three functional factor binding sites, an upstream HNF-3 site and a downstream overlapping AP-1/HNF-3 site (Sawaya, P.L., Stripp, B. R., Whitsett, J.A., and Luse, D. S. Mol. Cell. Biol. (1993) 13, 3860-3871). Fragments containing -320/+58 of the rat CCSP promoter were mutagenized to eliminate one or two factor binding sites in region I, cloned into a luciferase reporter cassette, and assayed for activity by transfection into cultured lung (H441) cells. We found that the HNF-3 sites alone can account for the activity of region I in H441 cells. The activity of the two HNF-3 sites is synergistic; this effect depends on the presence of an upstream factor binding site. We had shown previously that H441 cells contain exclusively the HNF-3 alpha form of HNF-3, whereas HeLa cells have essentially no HNF-3. Co-transfection of an HNF-3 alpha expression plasmid with a CCSP reporter containing four copies of region I in HeLa cells stimulated CCSP activity 4-fold, whereas co-expression of HNF-3 beta inhibited activity 8-fold. HNF-3 beta was also inhibitory to region I expression in H441 cells, but to a lesser extent than in HeLa cells, presumably because of the high levels of HNF-3 alpha already present in H441 cells. We have thus identified a gene regulatory element through which two members of the HNF-3 transcription factor family, HNF-3 alpha and HNF-3 beta, exert opposite effects.
 ...
PMID:Two members of the HNF-3 family have opposite effects on a lung transcriptional element; HNF-3 alpha stimulates and HNF-3 beta inhibits activity of region I from the Clara cell secretory protein (CCSP) promoter. 807 46

This study examines the effects of an ambient concentration of aged and diluted sidestream cigarette smoke (ADSS) on bronchiolar epithelial cell development and the expression of cytochrome P450 isozyme 1A1 protein in the postnatal rat lung. In control animals, the labeling indices for epithelial cells in proximal bronchi and terminal bronchioles at 7 days of age were 2.3 and 4.9%, respectively, and decreased to 0.1 and 0%, by 100 days of age. With exposure to ADSS from birth, the labeling index of epithelial cells in distal airways of rats was significantly reduced at 7 and 14 days of age, but not in epithelial cells of proximal bronchi. The expression of P450 isozyme 1A1 antigen in bronchiolar epithelial cells of control rats reached the maximal level observed at 21 days of age and subsequently decreased to low levels at 50 and 100 days of age. In contrast, exposure to ADSS significantly increased the distribution and intensity of staining for 1A1 antigen in bronchiolar epithelial cells of proximal and distal airways as early as 7 days of age and maintained elevated levels of 1A1 protein in these cells through 100 days of age. At 21 and 50 days of age, NADPH reductase protein expression was higher in the airway epithelium of rats exposed from birth to ADSS than that noted in the airways of controls. In contrast, cytochrome P450 isozyme 2B and Clara cell secretory protein expression were unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1994 Sep
PMID:Exposure to sidestream cigarette smoke alters bronchiolar epithelial cell differentiation in the postnatal rat lung. 808 68

The ypt2 gene of the fission yeast Schizosaccharomyces pombe encodes a member of the ypt/rab family of small GTP-binding proteins, related in sequence to Sec4p of Saccharomyces cerevisiae but closer to mammalian rab8. We have introduced a mutation into the gene corresponding to a mutation identified in ypt1, in which a conserved valine residue was altered to asparagine. The mutated ypt2 gene was introduced into the S. pombe genome by gene replacement. The resulting strain was temperature-sensitive for growth. Normal growth was restored by introduction of a plasmid-borne wild-type ypt2 cDNA or by cDNA for rab8 but not by various other rab or ypt sequences. At restrictive temperature the mutant cells accumulated the secretory protein acid phosphatase in a form that appeared to be fully glycosylated and acquired a population of vesicles detectable by electron microscopy. Thus the ypt2 protein, and by inference rab8, appear to function in the last stage of the secretory pathway.
Mol Biol Cell 1993 Oct
PMID:Function of the ypt2 gene in the exocytic pathway of Schizosaccharomyces pombe. 829 92

Uteroglobin (UG) is a hormonally regulated secretory protein produced in the lung and urogenital system of rabbits. It is homologous to rat and human Clara cell 10 kD protein (CC10); however, there are significant differences in the tissue-specific expression between these species. Mouse CC10 (mCC10) protein has been less well characterized. In this study, we cloned and sequenced the cDNA encoding the mCC10 protein. The mouse cDNA showed 90, 52, and 51% amino acid homology to rat and human CC10 and rabbit UG cDNA, respectively. The cellular and tissue-specific expression of mCC10 was examined in adult and developing mice. Endogenous mCC10 expression was compared with transgenic mice expressing a fusion gene of the rabbit 3.3 kb UG promoter linked to human growth hormone (hGH) as an easily detectable marker. Northern blot analysis detected mCC10 mRNA only in the lung. hGH mRNA was detected in the lung in levels similar to the endogenous mCC10 transcripts. However, it was also present in trace quantities in the uterus and ovary of normal adult female mice and in the epididymus of adult male mice. hGH and mCC10 proteins were identified in the trachea and lung, where they were localized to Clara cells. Ultrastructurally, hGH was present in secretory granules in the Clara cell cytoplasm and appeared to be secreted into the airways. hGH was initially detectable in 16 day gestation developing mice; however, CC10 was not detectable until the eighteenth day of gestation. We have created an attractive model for comparing the cis-acting DNA elements governing the interspecies variation in tissue-specific expression of CC10.
Am J Respir Cell Mol Biol 1993 Sep
PMID:Cloning and tissue-specific expression of the cDNA for the mouse Clara cell 10 kD protein: comparison of endogenous expression to rabbit uteroglobin promoter-driven transgene expression. 839 59


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>