Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

D. discoideum amoebae were found to phosphorylate plasma membrane proteins when intact cells were incubated with either [gamma-32P]ATP or [32P]phosphate. In the first case, the incorporation was largely a consequence of the hydrolysis of [gamma-32P]ATP, cellular uptake of the generated [32P]phosphate and its subsequent incorporation into ATP. When the contribution of this process to the phosphorylating activity of intact cells was eliminated, an ecto-protein kinase (ATP: protein phosphotransferase, EC 2.7.1.37) activity could be demonstrated. As amoebae progressed through their aggregation program, they showed a decreased ability to phosphorylate their plasma membrane when incubated with [gamma-32 P]ATP or [32P]phosphate. Analysis of ATPase activity, permeability properties and the pattern of proteins phosphorylated by intact cells and isolated plasma membranes lead to the following conclusions: the lower levels of phosphorylation observed with starved cells reflected an altered uptake of [32P]phosphate by these cells rather than a significant change in the plasma membrane protein kinase activity. Neither the substrates nor the activity of the ecto-protein kinase was dramatically altered during starvation.
 ...
PMID:A protein kinase of the plasma membrane of Dictyostelium discoideum. 731 41

The cdc2+ gene product (p34cdc2) is a protein kinase that regulates entry into mitosis in all eukaryotic cells. The role that p34cdc2 plays in the cell cycle has been extensively investigated in a number of organisms, including the fission yeast Schizosaccharomyces pombe. To study the degree of functional conservation among evolutionarily distant p34cdc2 proteins, we have constructed a S. pombe strain in which the yeast cdc2+ gene has been replaced by its Drosophila homologue CDC2Dm (the CDC2Dm strain). This CDC2Dm S. pombe strain is viable, capable of mating and producing four viable meiotic products, indicating that the fly p34CDC2Dm recognizes all the essential S. pombe cdc2+ substrates, and that it is recognized by cyclin partners and other elements required for its activity. The p34CDC2Dm protein yields a lethal phenotype in combination with the mutant B-type cyclin p56cdc13-117, suggesting that this S. pombe cyclin might interact less efficiently with the Drosophila protein than with its native p34cdc2 counterpart. This CDC2Dm strain also responds to nutritional starvation and to incomplete DNA synthesis, indicating that proteins involved in these signal transduction pathways, interact properly with p34CDC2Dm (and/or that p34cdc2-independent pathways are used). The CDC2Dm gene produces a 'wee' phenotype, and it is largely insensitive to the action of the S. pombe wee1+ mitotic inhibitor, suggesting that Drosophila wee1+ homologue might not be functionally conserved. This CDC2Dm strain is hypersensitive to UV irradiation, to the same degree as wee1-deficient mutants. A strain which co-expresses the Drosophila and yeast cdc2+ genes shows a dominant wee phenotype, but displays a wild-type sensitivity to UV irradiation, suggesting that p34cdc2 triggers mitosis and influences the UV sensitivity by independent mechanisms.
 ...
PMID:Functional analysis of the Drosophila CDC2 Dm gene in fission yeast. 747 62

A number of hormones and growth factors stimulate target cells through receptors which are coupled to second messenger pathways. The second messenger cAMP, for example, mediates a wide variety of cellular responses to hormonal signals, including changes in intermediary metabolism, cellular proliferation and cellular motility. In mammalian cells, all of these biological responses are triggered by the activation of the cAMP-dependent protein kinase A, a heterotetramer consisting of paired catalytic and regulatory subunits. Upon hormonal stimulation, cAMP binds tightly to the regulatory subunits, thereby liberating catalytic subunits and promoting the phosphorylation of cellular substrates. In the liver, cAMP functions as a starvation state signal, mediating hormonal cues from the pancreas and adrenal gland to stimulate glucose production. cAMP stimulates glucose production, in part, by regulating transcription of the gene for phosphoenolpyruvate carboxykinase (PEPCK), a rate-limiting enzyme in gluconeogenesis. Following hormonal stimulation, cAMP induces PEPCK gene expression 10-fold within 20-30 min. This induction appears to be independent of new protein synthesis.
 ...
PMID:Regulation of somatostatin gene transcription by cAMP. 758 54

Saccharomyces cerevisiae casein kinase II (CKII) contains two distinct catalytic (alpha and alpha') and regulatory (beta and beta') subunits. We report here the isolation and disruption of the gene, CKB1, encoding the 38-kDa beta subunit. The predicted Ckb1 sequence includes the N-terminal autophosphorylation site, internal acidic domain, and potential metal binding motif (CPX3C-X22-CPXC) present in other beta subunits but is unique in that it contains two additional autophosphorylation sites as well as a 30-amino-acid acidic insert. CKB1 is located on the left arm of chromosome VII, approximately 33 kilobases from the centromere and does not correspond to any previously characterized genetic locus. Haploid and diploid strains lacking either or both beta subunit genes are viable, demonstrating that the regulatory subunit of CKII is dispensable in S. cerevisiae. Such strains exhibit wild type behavior with regard to growth on both fermentable and nonfermentable carbon sources, mating, sporulation, spore germination, and resistance to heatshock and nitrogen starvation, but are salt-sensitive. Salt sensitivity is specific for NaCl and LiCl and is not observed with KCl or agents which increase osmotic pressure alone. These data suggest a role for CKII in ion homeostasis in S. cerevisiae.
 ...
PMID:Cloning and disruption of CKB1, the gene encoding the 38-kDa beta subunit of Saccharomyces cerevisiae casein kinase II (CKII). Deletion of CKII regulatory subunits elicits a salt-sensitive phenotype. 773 72

Regulation of the effective activity of eukaryotic initiation factor 2 (eIF-2) in protein synthesis is known to involve phosphorylation of its alpha subunit. Two mammalian enzymes, the haem-controlled repressor (HCR) and the double-stranded RNA-activated inhibitor (dsI), phosphorylate Ser-51 of the alpha subunit, thereby inhibiting the exchange of bound nucleotides on, and thus the recycling of, eIF-2. In Saccharomyces cerevisiae, the equivalent serine seems to be phosphorylated by the GCN2 protein kinase, which is activated by amino acid starvation. However, in the present paper we show that this is not the only site of phosphorylation in yeast eIF-2 alpha. We report the preparation of recombinant yeast eIF-2 alpha from Escherichia coli and its use in in vitro phosphorylation studies. Mammalian HCR and dsI are shown to phosphorylate specifically Ser-51 of yeast eIF-2 alpha, whereas extracts from yeast cells do not. Instead, at least one of three serine residue in the acidic C-terminal region of this protein is phosphorylated by fractions of yeast possessing casein kinase activities 1 and 2. A triple Ser-->Ala mutant form of yeast eIF-2 alpha was found to be no longer phosphorylated by either of the yeast (or mammalian) casein kinase activities in vitro. Isoelectric focusing of yeast extracts confirmed that the mutated sites normally act as sites of phosphorylation in vivo. The same mutant was used to show that the three sites have no essential function under normal physiological conditions in yeast. In contrast, deletion of the 13 amino acid long C-terminal region of eIF-2 alpha, including the three phosphorylation sites, led to derepression of GCN4 in vivo. Thus removal of the short, highly acidic C-terminal region of eIF-2 alpha has the same regulatory effect on translational (re)initiation as phosphorylation of the Ser-51 residue of the wild-type protein. This result provides new insight into the role of eIF-2 alpha activity in the regulation of translational (re-) initiation.
 ...
PMID:The highly acidic C-terminal region of the yeast initiation factor subunit 2 alpha (eIF-2 alpha) contains casein kinase phosphorylation sites and is essential for maintaining normal regulation of GCN4. 774 63

By differential hybridization, we identified a number of genes in Saccharomyces cerevisiae that are activated by addition of cyclic AMP (cAMP) to cAMP-depleted cells. A majority, but not all, of these genes encode ribosomal proteins. While expression of these genes is also induced by addition of the appropriate nutrient to cells starved for a nitrogen source or for a sulfur source, the pathway for nutrient activation of ribosomal protein gene transcription is distinct from that of cAMP activation: (i) cAMP-mediated transcriptional activation was blocked by prior addition of an inhibitor of protein synthesis whereas nutrient-mediated activation was not, and (ii) cAMP-mediated induction of expression occurred through transcriptional activation whereas nutrient-mediated induction was predominantly a posttranscriptional response. Transcriptional activation of the ribosomal protein gene RPL16A by cAMP is mediated through a upstream activation sequence element consisting of a pair of RAP1 binding sites and sequences between them, suggesting that RAP1 participates in the cAMP activation process. Since RAP1 protein decays during starvation for cAMP, regulation of ribosomal protein genes under these conditions may directly relate to RAP1 protein availability. These results define additional critical targets of the cAMP-dependent protein kinase, suggest a mechanism to couple ribosome production to the metabolic activity of the cell, and emphasize that nutrient regulation is independent of the RAS/cAMP pathway.
 ...
PMID:Nutrient availability and the RAS/cyclic AMP pathway both induce expression of ribosomal protein genes in Saccharomyces cerevisiae but by different mechanisms. 776 Aug 15

Cell differentiation and proliferation are mutually exclusive processes in many cases. The transition of starving Dictyostelium cells from growth to differentiation phase has been shown to occur at a particular position (putative shift point; PS-point) in the cell cycle of D. discoideum Ax-2. The significance of phosphorylation states of proteins such as 101 kDa, 90 kDa, and 32 kDa phosphoproteins has been argued, particularly around the PS-point. In this study we examined effects of the protein kinase inhibitors and activators on the transition of Ax-2 cells from growth to differentiation. K252a, a potent inhibitor of protein kinases, inhibited growth possibly through the blockage of pinocytotic activity of cells, and promoted the progress of development after starvation when applied to Ax-2 cells at the growth phase. Such a K252a-effect was most pronouncedly exhibited on the cells located near the PS-point. Unexpectedly, however, the development of starved cells was found to be considerably delayed by staurosporine bearing a structural and functional resemblance to K252a when it was applied during the growth phase. Pulse-labelings of growing Ax-2 cells with inorganic 32P (32Pi) showed that K252a induces the disappearance of a 48 kDa phosphoprotein and the appearance of a 50 kDa phosphoprotein, specifically in the cells located around the PS-point. Phosphorylation of 32 kDa and 24 kDa proteins was also inhibited by K252a, but this inhibition was not necessarily specific to the K252a-treatment and occurred independently of the cell-cycle phases. The possible significance of these results is discussed in relation to a breakaway of cells from proliferation to differentiation at the PS-point.
 ...
PMID:K252a, a potent inhibitor of protein kinases, promotes the transition of Dictyostelium cells from growth to differentiation. 776 85

The branched-chain alpha-ketoacid dehydrogenase (BCKDH) and pyruvate dehydrogenase (PDH) complexes are regulated by phosphorylation cycles catalyzed by complex-specific protein kinases and phosphoprotein phosphatases. Molecular cloning of these mitochondrial protein kinases has established a new family of protein kinases in eukaryotes that appears related by primary sequence to the histidine protein kinase family of prokaryotes. Changes in the activities of both kinases that are stable, i.e., not caused directly by allosteric effectors, correlate inversely with the changes in the activity states of the complexes that occur in different nutritional states. For example, BCKDH kinase activity is increased and the BCKDH complex activity state is decreased in rats fed diets deficient in protein. The increase in BCKDH kinase activity is due to an increase in the amount of BCKDH kinase protein bound to the BCKDH complex. The message level for BCKDH kinase also increases in the liver of rats starved for protein, suggesting a pretranslational mechanism exists for the long-term regulation of BCKDH kinase. Starvation and high-fat feeding cause a stable increase in PDH kinase activity and a corresponding decrease in activity state of the PDH complex. The mechanism responsible has not been defined.
 ...
PMID:Nutritional regulation of the protein kinases responsible for the phosphorylation of the alpha-ketoacid dehydrogenase complexes. 778 41

The SNF1 protein kinase is required for the regulatory response to glucose starvation in Saccharomyces cerevisiae. SNF1 is a protein serine/threonine kinase that has been widely conserved in both plants and mammals. Previously, we identified SIP1 and SIP2 as proteins that interact with SNF1 in vivo by the two-hybrid system. We have cloned the SIP2 gene and the encoded protein is homologous to SIP1 and to GAL83, which affects glucose repression of the GAL genes. We show that SIP2 and GAL83, like SIP1, co-immunoprecipitate with SNF1 and are phosphorylated in vitro. An 80 amino acid sequence, designated the ASC domain, is highly conserved at the C-termini of all three proteins. We show that this small domain can mediate protein-protein interaction with the SNF1 kinase complex. Thus, SIP1, SIP2 and GAL83 define a family of homologous proteins that are tightly associated with the SNF1 kinase, probably in alternative forms of the complex. Genetic evidence suggests that the three proteins have distinct, but related, functions in the SNF1 pathway, and deletion of GAL83 dramatically reduces SNF1 activity in immune complex assays. We propose that SIP1, SIP2 and GAL83 act as adaptors that promote the activity of SNF1 towards specific targets.
 ...
PMID:A family of proteins containing a conserved domain that mediates interaction with the yeast SNF1 protein kinase complex. 781 28

The PHO81 gene is thought to encode an inhibitor of the negative regulators (Pho80p and Pho85p) in the phosphatase (PHO) regulon. Transcription of PHO81 is regulated by Pi signals through the same PHO regulatory system. Elimination of the PHO81 promoter or its substitution by the GAL1 promoter revealed that stimulation of the PHO regulatory system requires both increased transcription of PHO81 and a Pi starvation signal. The predicted Pho81p protein contains 1,179 amino acids (aa) and has six repeats of an ankyrin-like sequence in its central region. The minimum amino acid sequence required for Pho81p function was narrowed down to a 141-aa segment (aa 584 to 724), which contains the fifth and sixth repeats of the ankyrin-like motif. The third to sixth repeats of the ankyrin-like motif of Pho81p have significant similarities to that of p16INK4, which inhibits activity of the human cyclin D-CDK4 kinase complex. Deletion analyses revealed that the N- and C-terminal regions of Pho81p behave as negative and positive regulatory domains, respectively, for the minimal 141-aa region. The negative regulatory activity of the N-terminal domain was antagonized by a C-terminal segment of Pho81p supplied in trans. All four known classes of PHO81c mutations that show repressible acid phosphatase activity in high-Pi medium affect the N-terminal half of Pho81p. An in vitro assay showed that a glutathione S-transferase-Pho81p fusion protein inhibits the Pho85p protein kinase. Association of Pho81p with Pho85p or with the Pho80p-Pho85p complex was demonstrated by the two-hybrid system.
 ...
PMID:Functional domains of Pho81p, an inhibitor of Pho85p protein kinase, in the transduction pathway of Pi signals in Saccharomyces cerevisiae. 782 64


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