Biochemical similarity of <i>Schizosaccharomyces pombe</i> ras1 protein with RAS2 protein of <i>Saccharomyces cerevisiae</i>

Onozawa, Takashi; Danjoh, Inaho; Fujiyama, Asao

doi:10.1002/yea.320110902

Cited by 17 publications

(2 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Its role in the delicate integration of signaling cascades is underscored by the occurrence of variants to the normal flow of information. These include protein kinases that can use GTP and small GTPases that can hydrolyze ATP (11,24). The large spectrum of ATP/GTP values achieved with our models will permit the evaluation of the role of this ratio in epithelial biology.…”

Section: Discussionmentioning

confidence: 99%

Modeling ischemia in vitro: selective depletion of adenine and guanine nucleotide pools

Dagher

2000

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

Intracellular ATP depletion is a hallmark event in ischemic injury. It has been extensively characterized in models of chemical anoxia in vitro. In contrast, the fate of GTP during ischemia remains unknown. We used LLC-PK proximal tubular cells to measure GTP and ATP changes during anoxia. In 45 min, antimycin A decreased ATP and GTP to 8% and 2% of controls, respectively. Ischemia in vivo resulted in comparable reductions in GTP and ATP. After 2 h of recovery, GTP levels in LLC-PK cells increased to 65% while ATP increased to 29%. We also investigated steady-state models of selective ATP or GTP depletion. Combinations of antimycin A and mycophenolic acid selectively reduced GTP to 51% or 25% of control. Similarly, alanosine selectively reduced ATP to 61% or 26% of control. Selective GTP depletion resulted in significant apoptosis. Selective ATP depletion caused mostly necrosis. These models of ATP or GTP depletion can prove useful in dissecting the relative contribution of the two nucleotides to the ischemic phenotype.

show abstract

Section: Discussionmentioning

confidence: 99%

Modeling ischemia in vitro: selective depletion of adenine and guanine nucleotide pools

Dagher

2000

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

show abstract

“…There are numerous examples of protein kinases that use GTP as substrate as well as ATP (Cochet et al, 1981;Pelech et al, 1987;Putnam-Evans et al, 1990;Stoehr and Smolen, 1990;Yamashita et al, 1992;Hide et al, 1994). Two ras-related GTPases have been described that bind and hydrolyze ATP Uritani and Miyazaki, 1988;Onozawa et al, 1995), and for one of them, ras1p of S. pombe, the possibility of ATP serving as an important effector has been discussed (Onozawa et al, 1995). It would be more surprising if signaling enzymes of this type did not exist, and in fact, more than anything else, the ATP phosphotransfer-GTP hydrolysis rule may actually reflect the fact that the nucleotide substrate specificity of many proteins described in cellular signaling has not been investigated.…”

Section: Candidates For Sensors Of P53/impd-dependentmentioning

confidence: 99%

Inosine-5′-Monophosphate Dehydrogenase Is a Rate-determining Factor for p53-dependent Growth Regulation

Liu

Bohn

Sherley

1998

MBoC

View full text Add to dashboard Cite

We have proposed that reduced activity of inosine-5Ј-monophosphate dehydrogenase (IMPD; IMP:NAD oxidoreductase, EC 1.2.1.14), the rate-limiting enzyme for guanine nucleotide biosynthesis, in response to wild-type p53 expression, is essential for p53-dependent growth suppression. A gene transfer strategy was used to demonstrate that under physiological conditions constitutive IMPD expression prevents p53-dependent growth suppression. In these studies, expression of bax and waf1, genes implicated in p53-dependent growth suppression in response to DNA damage, remains elevated in response to p53. These findings indicate that under physiological conditions IMPD is a rate-determining factor for p53-dependent growth regulation. In addition, they suggest that the impd gene may be epistatic to bax and waf1 in growth suppression. Because of the role of IMPD in the production and balance of GTP and ATP, essential nucleotides for signal transduction, these results suggest that p53 controls cell division signals by regulating purine ribonucleotide metabolism. INTRODUCTIONBeyond being the basic units of nucleic acids, nucleotides are ubiquitous molecular regulators. Nucleotides modulate diverse cellular processes by noncovalent allosteric regulation; covalent chemical activation via cleavage of high-energy phosphate bonds; covalent transfer of modulatory phosphate moieties; and providing the high energy output of phosphate bond cleavage for macromolecular conformational changes (Lehninger, 1975). Although many of the processes controlled by nucleotides are specific to their own biosynthesis and metabolism, they regulate a variety of other cellular processes as well (Lehninger, 1973;Criss and Pradhan, 1976;Pall, 1985).Adenine and guanine ribonucleotides are the most frequently used nucleotides for molecular regulation, functioning to modulate important biochemical reactions in all aspects of cell function (Pall, 1985). Our interest in ATP and GTP as molecular regulators relates to their function as essential components of growth signal transduction pathways. Interestingly, in cellular signaling, ATP-dependent and GTP-dependent mechanisms appear to be restricted to one of two distinct phosphate cleavage reactions. ATP mechanisms employ covalent phosphoryltransfer (reviewed in Sibley et al., 1987;Aaronson, 1991;Cantley et al., 1991;Hunter, 1995), whereas GTP mechanisms use phosphate hydrolysis (reviewed in Reed, 1990;Simon et al., 1991;Hall, 1992;Chant and Stowers, 1995). Phosphoryltransfer modifies the catalytic or association properties of signaling molecules, whereas the energy of phosphate hydrolysis fuels structural rearrangements that lead to activation of GTP-bound proteins. Effectors of the balance of these distinct regulatory mechanisms may be important factors for integrated regulation of cellular growth signals.Given the importance of ATP and GTP in signal transduction, their metabolism may be an important factor for cellular signaling (Pall and Robertson, 1988;Sherley, 1991). However, effects of nucleotide metabolism...

show abstract

Ras-mediated signaling pathway regulates the expression of a low-molecular-weight heat-shock protein in fission yeast

Danjoh

Fujiyama

1999

Gene

View full text Add to dashboard Cite

Biochemical similarity of Schizosaccharomyces pombe ras1 protein with RAS2 protein of Saccharomyces cerevisiae

Cited by 17 publications

References 27 publications

Modeling ischemia in vitro: selective depletion of adenine and guanine nucleotide pools

Modeling ischemia in vitro: selective depletion of adenine and guanine nucleotide pools

Inosine-5′-Monophosphate Dehydrogenase Is a Rate-determining Factor for p53-dependent Growth Regulation

Ras-mediated signaling pathway regulates the expression of a low-molecular-weight heat-shock protein in fission yeast

Contact Info

Product

Resources

About