Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Activating mutations (valine 19 or leucine 68) were introduced into the Saccharomyces cerevisiae RAS1 and RAS2 genes. In addition, a deletion was introduced into the wild-type gene and into an activated RAS2 gene, removing the segment of the coding region for the unique C-terminal domain that lies between the N-terminal 174 residues and the penultimate 8-residue membrane attachment site. At low levels of expression, a dominant activated phenotype, characterized by low glycogen levels and poor sporulation efficiency, was observed for both full-length RAS1 and RAS2 variants having impaired GTP hydrolytic activity. Lethal CDC25 mutations were bypassed by the expression of mutant RAS1 or RAS2 proteins with activating amino acid substitutions, by expression of RAS2 proteins lacking the C-terminal domain, or by normal and oncogenic mammalian Harvey ras proteins. Biochemical measurements of adenylate cyclase in membrane preparations showed that the expression of RAS2 proteins lacking the C-terminal domain can restore adenylate cyclase activity to cdc25 membranes.
 ...
PMID:Regulatory function of the Saccharomyces cerevisiae RAS C-terminus. 330 71

The CDC25 Start gene whose product appears to be required for traversing the Go phase of the cell cycle in Saccharomyces cerevisiae, has been previously cloned (J. Daniel and G. Simchen (1986), Curr Genet 10:643-646). By nucleotide sequencing of an active subclone, we found that only a region of the gene that codes for the C-terminal portion of the CDC25 protein was required for full suppression of the cdc25 mutation. The codon usage in this region indicates a poor translation of the transcript compared to genes encoding abundant proteins. The derived CDC25 protein fragment contains two regions of homology, one with the rhodopsin family, the other with the cytochrome P450 family. Strikingly, these two regions of homology are adjacent on the CDC25 protein. In view of the likely involvement of the CDC25 protein in the regulation of adenylate cyclase activity, a working hypothesis is proposed that accounts for the observed homologies.
 ...
PMID:The CDC25 "Start" gene of Saccharomyces cerevisiae: sequencing of the active C-terminal fragment and regional homologies with rhodopsin and cytochrome P450. 332 37

We have cloned the CDC25 gene of Saccharomyces cerevisiae whose product is required for traversing the Go phase of the cell cycle. A preliminary physical characterization of the CDC25 gene region is presented. In addition, we show that another gene, when cloned in a high-copy number plasmid, is able to partially suppress growth thermosensitivity of a strain carrying the cdc25 mutation. We briefly discuss the possible interaction of these gene products with adenylate cyclase encoded by the CDC35 gene.
 ...
PMID:Clones from two different genomic regions complement the cdc25 start mutation of Saccharomyces cerevisiae. 332 39

The gene corresponding to the S. cerevisiae cell division cycle mutant cdc25 has been cloned and sequenced, revealing an open reading frame encoding a protein of 1589 amino acids that contains no significant homologies with other known proteins. Cells lacking CDC25 have low levels of cyclic AMP and decreased levels of Mg2+-dependent adenylate cyclase activity. The lethality resulting from disruption of the CDC25 gene can be suppressed by the presence of the activated RAS2val19 gene, but not by high copy plasmids expressing a normal RAS2 or RAS1 gene. These results suggest that normal RAS is dependent on CDC25 function. Furthermore, mutationally activated alleles of CDC25 are capable of inducing a set of phenotypes similar to those observed in strains containing a genetically activated RAS/adenylate cyclase pathway, suggesting that CDC25 encodes a regulatory protein. We propose that CDC25 regulates adenylate cyclase by regulating the guanine nucleotide bound to RAS proteins.
 ...
PMID:The S. cerevisiae CDC25 gene product regulates the RAS/adenylate cyclase pathway. 354 97

The yeast Saccharomyces cerevisiae contains two functional homologues of the ras oncogene family, RAS1 and RAS2. These genes are required for growth, and all evidence indicates that this essential function is the activation of adenylate cyclase. In contrast, ras in mammalian cells does not appear to influence adenylate cyclase activity. To clarify the relation between ras function in yeast and in higher eukaryotes, and the role played by yeast RAS in growth control, it is necessary to identify functions acting upstream of RAS in the adenylate cyclase pathway. The evidence presented here indicates that CDC25, identified by conditional cell cycle arrest mutations, encodes such an upstream function.
 ...
PMID:CDC25: a component of the RAS-adenylate cyclase pathway in Saccharomyces cerevisiae. 354 48

Two isofunctional ras genes are present in the yeast Saccharomyces cerevisiae. Albeit their targets differ between mammals and yeast, they have conserved their regulators. The study of their positive regulators, guanine nucleotide exchange factors, have provided routes to the discovery of their regulatory elements in mammals. Ras are signal transducing proteins involved in the activation of the adenylate cyclase in yeast. They are activated by Cdc25p which has been shown to contain a Guanine Exchange Factor domain (GEF). SDC25, a gene partially homologous to CDC25, also contains a GEF domain but seems to be under a different regulation. It has been used to demonstrate the first guanine exchange activity on ras in vitro and was shown to be active by gene transfer in mammalian cells. Both Cdc25p and Sdc25p are associated to membrane and contain SH3 domains which are supposed to bind still unidentified proteins. Cdc25p is an unstable protein which contains a cyclin destruction box. Therefore activating effect on ras could be regulated by its level of expression. We have contributed to the isolation of a mammalian CDC25 homolog and we are analysing by directed mutagenesis key positions for ras activation of the human homolog HGRF55. That was performed by complementation analysis of yeast mutants as well as by use of two hybrid system. These approaches led us to the discovery of residues involved in ras interaction.
 ...
PMID:[Yeast and the control of RAS by exchange factors]. 764 64

Two C-terminal fragments (334 and 509 amino acid residues) of CDC25, a Saccharomyces cerevisiae GDP/GTP exchange factor, and the RAS2 protein were purified from E. coli, using the pGEX system. With this method it was possible to avoid in part the proteolytic phenomena that usually convert full-length RAS2 (42kDa) into 37 and 30kDa forms. Of the two CDC25 fragments containing the conserved catalytic domain, only CDC25-509 could enhance the guanine nucleotide exchange on RAS2. Comparison of the activities of RAS2-42/37kDa and RAS2-30kDa showed that the C-terminal region (112 residues) influences neither the intrinsic GDP/GTP exchange nor its stimulation by CDC25-509. RAS2-42/37kDa was somewhat more effective in enhancing the adenylylcyclase activity of a yeast membrane reconstituted system. CDC25-509 displayed a higher specific activity than the catalytic domains of the two CDC25-like proteins: S. cerevisiae SDC25 and mouse CDC25Mm.
 ...
PMID:Properties of the catalytic domain of CDC25, a Saccharomyces cerevisiae GDP/GTP exchange factor: comparison of its activity on full-length and C-terminal truncated RAS2 proteins. 813 91

In the budding yeast Saccharomyces cerevisiae cyclic AMP (cAMP) can influence the activity of key enzymes in carbohydrate metabolism through modulation of the activity of cAMP-dependent protein kinase. One of the components involved in cAMP production is the CDC25 gene product, which can activate the RAS/adenylate cyclase pathway by promoting the exchange of guanine nucleotides bound to RAS. In two yeast strains carrying different thermosensitive alleles of the CDC25 gene, cAMP levels respond differently to an increase in growth temperature from 23 degrees C (permissive) to 36 degrees C (restrictive). In strain OL86 (cdc25-5) the estimated intracellular concentration of cAMP dropped after transfer to restrictive temperature whereas in strain ts321 (cdc25-1) the cAMP level rose under the same conditions. Despite the differences in cAMP levels the glycolytic flux in the two mutants responded in a very similar way to the shift from permissive to restrictive temperature; after the increase in the incubation temperature, the specific glycolytic flux in both cdc25-1 and cdc25-5 initially increased from about 300 nmol min-1 (mg protein)-1 to about 500 nmol min-1 (mg protein)-1 (presumably mainly as a consequence of the increase in temperature), but then gradually fell to 100-200 nmol min-1 (mg protein)-1. A similar pattern of CO2 production to that found in the two cdc25 mutants was also observed for several other thermosensitive mutants displaying a Start-II type of G1 arrest. In contrast, in a wild-type strain and in strains giving a Start-I type of G1 arrest, CO2 production did not drop after a temperature shift. The specific activities of glycolytic enzymes in the two cdc25 mutants did not show much change after the temperature shift, indicating that the decrease in glycolytic flux was not caused by a decrease in the activity of any of the glycolytic enzymes. Our data show that, at least in long-term regulation, the cAMP levels per se are not likely to be a prime factor controlling glycolytic flux.
 ...
PMID:Inactivation of the CDC25 gene product in Saccharomyces cerevisiae leads to a decrease in glycolytic activity which is independent of cAMP levels. 824 36

Levels of cyclic 3',5'-cyclic monophosphate (cAMP) play an important role in the decision to enter the mitotic cycle in the yeast, Saccharomyces cerevisiae. In addition to growth arrest at stationary phase, S. cerevisiae transiently arrest growth as they shift from fermentative to oxidative metabolism (the diauxic shift). Experiments examining the role of cAMP in growth arrest at the diauxic shift show the following: 1) yeast lower cAMP levels as they exhaust their glucose supply and shift to oxidative metabolism of ethanol, 2) a reduction in cAMP is essential for traversing the diauxic shift, 3) the decrease in adenylate cyclase activity is associated with a decrease in the expression of CYR1 and CDC25, two positive regulators of cAMP levels and an increase in the expression of IRA1 and IRA2, two negative regulators of intracellular cAMP, 4) mutants carrying disruptions in IRA1 and IRA2 were unable to arrest cell division at the diauxic shift and were unable to progress into the oxidative phase of growth. These results indicate that changes cAMP levels are important in regulation of growth arrest at the diauxic shift and that changes in gene expression plays a role in the regulation of the Ras/adenylate cyclase system.
 ...
PMID:Changes in gene expression in the Ras/adenylate cyclase system of Saccharomyces cerevisiae: correlation with cAMP levels and growth arrest. 840 Apr 61

The activation of adenylate cyclase by guanine nucleotides and 6-deoxyglucose was studied in membrane preparations from S. cerevisiae mutants lacking the CDC25 gene product. Adenylate cyclase from cdc25 ts membranes was activated by GTP and GppNHp in membranes from cells collected after glucose was exhausted from the medium. The activation was also observed in membranes from repressed cells at 2.5 mM Mg2+. It is also shown that 6-deoxyglucose can activate adenylate cyclase in the absence of CDC25 gene product. The relative amount of membrane-bound adenylate cyclase was drastically reduced in cdc25 ts membranes when subjected to the restrictive temperature, while no significant change was observed in the wild type. These data suggest that Cdc25 might not be required in certain conditions for the guanine nucleotide exchange reaction in Ras and that it might be implicated in anchoring the Ras/adenylate cyclase system to the plasma membrane.
 ...
PMID:Activation of adenylate cyclase in cdc25 mutants of Saccharomyces cerevisiae. 845 16


<< Previous 1 2 3 4 Next >>