Cyclic AMP-Independent Regulation of Protein Kinase A Substrate Phosphorylation by Kelch Repeat Proteins

Lu, Ailan; Hirsch, Jeanne P.

doi:10.1128/ec.4.11.1794-1800.2005

Cited by 37 publications

(39 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Also, although cAMP and glycogen oscillated when the cells were grown on glucose, no oscillation was observed in these metabolites when the cells were grown on ethanol media (38 and D.B.M., unpublished data). This finding does not rule out a role for the PKA pathway in controlling the respiratory oscillation because the TOR complex 1 and PKA signaling pathways cross-talk (39), and the PKA pathway can be phosphorylated independently of cAMP (40). The mechanistic elucidation of these transcriptional regulators is needed to elucidate their role during oscillatory dynamics.…”

Section: Discussionmentioning

confidence: 99%

Regulation of yeast oscillatory dynamics

Murray

Beckmann

Kitano

2007

Proc. Natl. Acad. Sci. U.S.A.

136

151

View full text Add to dashboard Cite

When yeast cells are grown continuously at high cell density, a respiratory oscillation percolates throughout the population. Many essential cellular functions have been shown to be separated temporally during each cycle; however, the regulatory mechanisms involved in oscillatory dynamics remain to be elucidated. Through GC-MS analysis we found that the majority of metabolites show oscillatory dynamics, with 70% of the identified metabolite concentrations peaking in conjunction with NAD(P)H. Through statistical analyses of microarray data, we identified that biosynthetic events have a defined order, and this program is initiated when respiration rates are increasing. We then combined metabolic, transcriptional data and statistical analyses of transcription factor activity, identified the top oscillatory parameters, and filtered a large-scale yeast interaction network according to these parameters. The analyses and controlled experimental perturbation provided evidence that a transcriptional complex formed part of the timing circuit for biosynthetic, reductive, and cell cycle programs in the cell. This circuitry does not act in isolation because both have strong translational, proteomic, and metabolic regulatory mechanisms. Our data lead us to conclude that the regulation of the respiratory oscillation revolves around coupled subgraphs containing large numbers of proteins and metabolites, with a potential to oscillate, and no definable hierarchy, i.e., heterarchical control. metabolic regulation ͉ respiratory oscillation ͉ temporal structure ͉ transcriptional regulation ͉ self-organization A s we obtain a greater understanding of systems dynamics, it is becoming apparent that biological oscillators play critical roles in the organization of physiology in all time scales, ranging from milliseconds to years (1, 2). At the end of yeast growth in batch culture, there is series of cycles in respiratory activity that occur before the culture entering stationary phase (3). When continuous culture is initiated, the culture can be maintained in this oscillatory state [40 min to 5 h; see supporting information (SI) Fig. 5] for months (4-6). These dynamics result in the temporal separation of many essential cellular functions, including redox biochemistry (7,8), transcription (9, 10), energetics (11), chromosome cycle (1), and mitochondrial function (5). Although respiration is always active, the cellular redox state cycles between an oxidative phase and reductive phase. It is known that at least two redox active compounds, acetaldehyde and H 2 S, mediate cell-cell communication (12), but little is known regarding how synchrony is generated within the cell and how the network is regulated.A major problem in elucidating the oscillatory mechanism is the extent to which the cellular network is entrained, i.e., in a system where the majority of parameters oscillate how does one pull out core mechanisms. Fortunately, Saccharomyces cerevisiae has been used extensively as a proving ground for many of the new low-and high-throughpu...

show abstract

Section: Discussionmentioning

confidence: 99%

Regulation of yeast oscillatory dynamics

Murray

Beckmann

Kitano

2007

Proc. Natl. Acad. Sci. U.S.A.

136

151

View full text Add to dashboard Cite

show abstract

“…The kelch-repeat proteins interact with Gpa2 and contain seven kelch repeats that mimic the b propeller that is formed by seven WD-40 repeats in canonical G b subunits. Phenotypic analysis of gpb1D gpb2D double deletion mutants showed that the kelch-repeat proteins act as negative regulators of PKA signalling (Harashima and Heitman 2002;Batlle et al 2003;Lu and Hirsch 2005). Several mechanisms have been proposed to explain their effect.…”

Section: Regulation Of the Camp-pka Pathwaymentioning

confidence: 99%

Life in the midst of scarcity: adaptations to nutrient availability in Saccharomyces cerevisiae

et al. 2010

View full text Add to dashboard Cite

Cells of all living organisms contain complex signal transduction networks to ensure that a wide range of physiological properties are properly adapted to the environmental conditions. The fundamental concepts and individual building blocks of these signalling networks are generally well-conserved from yeast to man; yet, the central role that growth factors and hormones play in the regulation of signalling cascades in higher eukaryotes is executed by nutrients in yeast. Several nutrient-controlled pathways, which regulate cell growth and proliferation, metabolism and stress resistance, have been defined in yeast. These pathways are integrated into a signalling network, which ensures that yeast cells enter a quiescent, resting phase (G 0 ) to survive periods of nutrient scarceness and that they rapidly resume growth and cell proliferation when nutrient conditions become favourable again. A series of well-conserved nutrient-sensory protein kinases perform key roles in this signalling network: i.e. Snf1, PKA, Tor1 and Tor2, Sch9 and Pho85-Pho80. In this review, we provide a comprehensive overview on the current understanding of the signalling processes mediated via these kinases with a particular focus on how these individual pathways converge to signalling networks that ultimately ensure the dynamic translation of extracellular nutrient signals into appropriate physiological responses.

show abstract

“…Two kelchrepeat proteins, Gpb1 and Gbp2 (also known as Krh1 and Krh2), were proposed to function as the G␤ subunits for Gpa2 (34). However, further investigation has shown that these proteins are not G␤-mimics but instead function to inhibit signaling downstream of Gpa2 (21,(35)(36)(37). Using bioinformatic, genomic, biochemical, and pharmacological approaches we have identified Asc1 as the G␤ for Gpa2, and demonstrate a critical role for Asc1 in the glucose signaling pathway mediated by adenylyl cyclase.…”

mentioning

confidence: 99%

The RACK1 Ortholog Asc1 Functions as a G-protein β Subunit Coupled to Glucose Responsiveness in Yeast

Zeller

Parnell

Dohlman

2007

Journal of Biological Chemistry

136

View full text Add to dashboard Cite

According to the prevailing paradigm, G-proteins are composed of three subunits, an ␣ subunit with GTPase activity and a tightly associated ␤␥ subunit complex. In the yeast Saccharomyces cerevisiae there are two known G␣ proteins (Gpa1 and Gpa2) but only one G␤␥, which binds only to Gpa1. Here we show that the yeast ortholog of RACK1 (receptor for activated protein kinase C1) Asc1 functions as the G␤ for Gpa2. As with other known G␤ proteins, Asc1 has a 7-WD domain structure, interacts directly with the G␣ in a guanine nucleotide-dependent manner, and inhibits G␣ guanine nucleotide exchange activity. In addition, Asc1 binds to the effector enzyme adenylyl cyclase (Cyr1), and diminishes the production of cAMP in response to glucose stimulation. Thus, whereas Gpa2 promotes glucose signaling through elevated production of cAMP, Asc1 has opposing effects on these same processes. Our findings reveal the existence of an unusual G␤ subunit, one having multiple functions within the cell in addition to serving as a signal transducer for cell surface receptors and intracellular effectors.

show abstract

Cyclic AMP-Independent Regulation of Protein Kinase A Substrate Phosphorylation by Kelch Repeat Proteins

Cited by 37 publications

References 41 publications

Regulation of yeast oscillatory dynamics

Regulation of yeast oscillatory dynamics

Life in the midst of scarcity: adaptations to nutrient availability in Saccharomyces cerevisiae

The RACK1 Ortholog Asc1 Functions as a G-protein β Subunit Coupled to Glucose Responsiveness in Yeast

Contact Info

Product

Resources

About