Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We used co-cultures of porcine ovarian granulosa cells and mouse adrenocortical tumor cells (Y-1) to examine the kinetics of contact-dependent intercellular signal transfer and to assess the molecular mechanisms employed by this process. Exposure to follicle-stimulating hormone (FSH) caused cAMP-dependent protein kinase dissociation in granulosa cells and, with time, in Y-1 cells if, and only if, they contacted a responding granulosa cell. Y-1 cells close to a granulosa cell but not touching it failed to respond similarly. In reciprocal experiments, co-cultures were stimulated with adrenocorticotropic hormone (ACTH). Y-1 cells dissociated protein kinase as did granulosa cells in contact with Y-1 cells; however, granulosa cells that were not in contact with Y-1 cells failed to respond to the hormone. Fluorogenic steroids were secreted by Y-1 cells cultured alone and stimulated with ACTH, but were not secreted by cultures exposed to FSH. Neither hormone caused fluorogenic steroid production by granulosa cells. On the other hand these steroids were secreted in co-cultures stimulated with ACTH and to a lesser degree in co-cultures exposed to FSH. Autoradiography revealed that I125-FSH bound only to granulosa cells, never to Y-1 cells, even if they were in contact with an ovarian cell. The possibility of cell fusion was tested by experiments in which Y-1 cell membranes were labeled with cationized ferritin. These cells were then placed in co-culture with ovarian granulosa cells that had previously been allowed to ingest latex spheres. At regions of gap junctions between Y-1 and granulosa cells ferritin remained attached to the adrenal cell membrane and was never observed to migrate to the granulosa cell membrane. From these data, we conclude that hormone specific stimulation of one cell type leads to protein kinase dissociation in heterotypic partners only if they contact a hormone responsive cell. This signal transfer is bidirectional, exhibits temporal kinetics and occurs in the absence of apparent cell fusion. The only structural feature connecting Y-1 and granulosa cells were gap junctions implying they provided the communication channels; however, alternative mechanisms cannot be excluded. We have not established the identity of the signal being transferred although cAMP is a logical candidate.
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PMID:Hormone-induced intercellular signal transfer dissociates cyclic AMP-dependent protein kinase. 632 20

Cell-specific differences occur in the primary structure of ferritin. For example, red cell and liver ferritin from bullfrog tadpoles differ by 1.5 times in serine content. To determine if cell-specific differences in ferritin primary structure are expressed in the tetraeicosomer, which thus might distinguish the proteins in a functional state, phosphorylation in vitro was employed as a probe using [gamma-32P]ATP and the catalytic subunit from the cAMP-dependent protein kinase of bovine skeletal muscle. Subunits of both proteins in the tetraeicosomers were phosphorylated. Based on tryptic peptide maps, five regions common to both red cell and liver apoferritin were phosphorylated, as confirmed for two peptides by amino acid analyses. [32P]Apoferritin from red cells yielded an additional four 32P-fragments by mapping, at least three of which were unique by amino acid analysis and, in one case, might represent a 32P-Fe complex bound by a fragment of the iron-binding site. One peptide appeared to be unique to liver apoferritin. High concentrations of ATP yielded one additional peptide common to liver and red cell and one red cell-specific peptide in the tryptic peptide maps. The maximum moles of 32P/molecule were 13 +/- 4 and 6 +/- 2, respectively, for red cell and liver apoferritin, which corresponded within experimental error to the number of 32P-tryptic peptides. The level of phosphorylation was, on the average, not more than one site/subunit. Furthermore, above certain levels of phosphorylation, some subunits in the assemblage of 24 appeared to be unavailable as substrates, possibly because of charge repulsion or conformational changes. The possibility that post-translational modifications of ferritin which amplify cell-specific structural features occur in vivo with cytoplasmic components, e.g. protein kinases, is considered in terms of the physiological availability of iron from different iron storage cells and developmental changes in iron storage.
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PMID:Cell-specific properties of red cell and liver ferritin from bullfrog tadpoles probed by phosphorylation in vitro. 660 21

Murine erythroleukemia cells rendered deficient in cAMP-dependent protein kinase (A-kinase) activity by gene transfection are severely impaired in hexamethylene bisacetamide (HMBA)-induced differentiation (Pilz, R. B., Eigenthaler, M., and Boss, G. R. (1992) J. Biol. Chem. 267, 16161-16167). We now demonstrate that the A-kinase-deficient cells produce hemoglobin normally in response to exogenous hemin and that the heme precursor delta-aminolevulinate (delta-ALA) significantly increases HMBA-induced synthesis of heme and globin chains in these cells; these data suggest that impaired heme synthesis is at least partially responsible for the cells' deficient hemoglobin synthesis. HMBA-induced expression of the erythroid-specific delta-ALA synthetase, porphobilinogen deaminase, and beta-globin mRNAs was less in A-kinase-deficient cells than in parental cells and was reduced in proportion to the cells' residual A-kinase activity; relative transcription rates of these genes were reduced concordantly. Impaired expression of these three erythroid-specific genes was a feature of many independently-derived A-kinase-deficient clones, and normal expression was found in transfectants with normal A-kinase activity. The A-kinase-deficient cells did not exhibit a generalized defect in gene regulation since mRNA expression and transcription rates of H- and L-ferritin, c-myc, c-myb, and several housekeeping enzymes were similar in HMBA-treated parental and A-kinase-deficient cells. Our data suggest that A-kinase may be involved in regulating genes with erythroid-specific promoters and provide further evidence for heme as a regulator of globin chain synthesis.
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PMID:Impaired erythroid-specific gene expression in cAMP-dependent protein kinase-deficient murine erythroleukemia cells. 837 86

In cultured rat hepatocytes the degradation of phosphoenolpyruvate carboxykinase mRNA might be regulated by protein(s), which by binding to the mRNA alter its stability. The 3'-untranslated region of phosphoenolpyruvate carboxykinase mRNA as a potential target was used to select RNA-binding protein(s) from rat liver by the use of gel retardation assays. A cytosolic protein was isolated, which bound to the phosphoenolpyruvate carboxykinase mRNA 3'-untranslated region and other in vitro synthesized RNAs. The protein was purified to homogeneity; it had an apparent molecular mass of 400 kDa and consisted of identical subunits with an apparent size of 24.5 kDa. Sequence analysis of a tryptic peptide from the 24.5-kDa protein revealed its identity with rat ferritin light chain. Binding of ferritin to RNA was abolished after phosphorylation with cAMP-dependent protein kinase and was augmented after dephosphorylation with alkaline phosphatase. Weak binding was observed in extracts from okadaic acid-treated cultured hepatocytes compared with untreated cells. Preincubation of ferritin with an anti-phosphoserine or an anti-phosphothreonine antibody attenuated binding to RNA, while an anti-phosphotyrosine antibody generated a supershift indicating that phosphoserine and phosphothreonine but not phosphotyrosine residues were in close proximity to the RNA-binding region. Ferritin is the iron storage protein in the liver. Binding of ferritin to RNA was diminished in the presence of increasing iron concentrations, whereas the iron chelator desferal was without effect. It is concluded that ferritin might function as RNA-binding protein and that it may have important functions in the general regulation of cellular RNA metabolism.
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PMID:Purification of a RNA-binding protein from rat liver. Identification as ferritin L chain and determination of the RNA/protein binding characteristics. 924

During food shortage, organisms activate defense mechanisms to maximize their chance of survival. At least in part, these responses are triggered by changes in hormonal status and neural status during starvation. The hypothalamus is organized as a collection of distinct autonomously active nuclei and is considered to play crucial roles in these survival responses. To isolate factors involved in these pathways, we carried out suppression subtractive hybridization analyses using complementary DNAs (cDNA) from the hypothalami of fasted and fed rats. We identified four genes, namely ubiquitin-conjugating enzyme E2D 3 (UBE2D3), cAMP-dependent protein kinase C beta subunit (PKCbeta), excitatory amino acid carrier 1 (EAAC1), and ferritin heavy polypeptide 1 (Fth1), that were upregulated after a 48-h fast compared to the fed status. According to previous reports, these genes have been implicated in protection against neuronal cell death under various neurodegenerative stresses, such as hypoxia-ischemia and oxidative stress. Thus, the increased expressions of the genes identified in the present study may have protective effects against neural damage that could otherwise result in cell death.
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PMID:Identification of fasting-induced genes in the rat hypothalamus: relationship with neuroprotection. 1805 70

ATF1 (activating transcription factor 1), a stimulus-induced CREB family transcription factor, plays important roles in cell survival and proliferation. Phosphorylation of ATF1 at Ser63 by PKA (cAMP-dependent protein kinase) and related kinases was the only known post-translational regulatory mechanism of ATF1. Here, we found that HIPK2 (homeodomain-interacting protein kinase 2), a DNA-damage-responsive nuclear kinase, is a new ATF1 kinase that phosphorylates Ser198 but not Ser63. ATF1 phosphorylation by HIPK2 activated ATF1 transcription function in the GAL4-reporter system. ATF1 is a transcriptional repressor of ferritin H, the major intracellular iron storage gene, through an ARE (antioxidant-responsive element). HIPK2 overrode the ATF1-mediated ARE repression in a kinase-activity-dependent manner in HepG2 cells. Furthermore, DNA-damage-inducing agents doxorubicin, etoposide and sodium arsenite induced ferritin H mRNA expression in HIPK2(+/+) MEF cells, whereas it was significantly impaired in HIPK2(-/-) MEF cells. Induction of other ARE-regulated detoxification genes such as NQO1 (NADPH quinone oxidoreductase 1), GST (glutathione S-transferase) and HO1 (heme oxygenase 1) by genotoxic stress was also decreased in HIPK2-deficient cells. Taken together, these results suggest that HIPK2 is a new ATF1 kinase involved in the regulation of ferritin H and other antioxidant detoxification genes in genotoxic stress conditions.
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PMID:Transcriptional regulation of ferritin and antioxidant genes by HIPK2 under genotoxic stress. 2098 Mar 92