MINIREVIEW
New aspects on phosphate sensing and signalling in Saccharomyces
cerevisiae
Jean-Marie Mouillon & Bengt L. Persson
Department of Chemistry and Biomedical Sciences, Kalmar University, Kalmar, Sweden
Correspondence: Bengt Persson, Norra
vagen 49, Kalmar S-39182, Sweden. Tel.:
146 480 446276; fax: 146 480 446262;
e-mail: [email protected]
Received 7 October 2005; revised 27 October
2005; accepted 3 November 2005.
First published online 10 January 2006.
doi:10.1111/j.1567-1364.2006.00036.x
Editor: Lex Scheffers
Keywords
phosphate sensing and signalling; PHO
pathway; protein kinase; Saccharomyces
cerevisiae.
Abstract
The mechanism involved in the cellular phosphate response of Saccharomyces
cerevisiae forms part of the PHO pathway, which upon expression allows a coordinated cellular response and adaptation to changes in availability of external
phosphate. Although genetic studies and analyses of the S. cerevisiae genome have
produced much information on the components of the PHO pathway, little is
known about how cells sense the environmental phosphate level and the mechanistic regulation of phosphate acquisition. Recent studies emphasize different levels
in phosphate sensing and signalling in response to external phosphate fluctuations.
This review integrates all these findings into a model involving rapid and longterm effects of phosphate sensing and signalling in S. cerevisiae. The model
describes in particular how yeast cells are able to adjust phosphate acquisition by
integrating the status of the intracellular phosphate pools together with the
extracellular phosphate concentration.
Introduction
The metabolism of Saccharomyces cerevisiae is highly adaptable and allows cells to respond to changes in environmental factors such as nutrient status, pH and salinity. A rapid
response and quick adaptation to such environmental stress
is thus essential for cell survival. In S. cerevisiae, the
mechanism involved in the cellular phosphate response
forms part of a complex cascade pathway, the PHO pathway,
a genetic regulatory circuit, which allows a co-ordinated
cellular response and adaptation to changes in availability of
external free phosphate (Pi) (Lenburg & O’Shea, 1996;
Oshima, 1997; Persson et al., 2003). The cellular adaptation
to phosphate limitation and surplus conditions also requires
that the prevailing phosphate concentration is ‘sensed’ by
the cells. Although genetic studies and analyses of the S.
cerevisiae genome have produced much information on the
components of the PHO pathway, little is known about how
cells sense the environmental Pi level and the mechanistic
regulation of carrier-mediated Pi acquisition. Recently,
Giots et al. (2003) have shown that addition of phosphate
to severely phosphate-starved yeast cells activates the protein kinase A (PKA) signalling pathway. Although the
mechanisms that induce PKA activity in response to Pi
FEMS Yeast Res 6 (2006) 171–176
sensing and signalling have not yet been elucidated, these
findings demonstrate existing molecular links between glucose- and phosphate-signalling pathways. This review will
emphasize recent data obtained on phosphate sensing and
signalling in yeast and attempt to provide a new model on
how yeast adapts to environmental phosphate changes by
both rapid and long-term responses.
The PHO pathway is activated via
intracellular phosphate sensing
The PHO pathway mediates the phosphate response by
controlling the activity and localization of the transcription
factor Pho4 through phosphorylation by the cyclin-dependent kinase (CDK) complex Pho80–Pho85 (Toh-e et al.,
1988). When cells are starved of phosphate, the CDK
inhibitor Pho81 inactivates Pho80–Pho85, thereby allowing
unphosphorylated Pho4 to associate with the nuclear import receptor Pse1 and to enter the nucleus to induce
expression of several genes (Fig. 1; Vogel et al., 1989; Kaffman et al., 1994). Expression of genes coding for the highaffinity transport system (PHO84, PHO89), the secreted
acid phosphatases (PHO5, PHO11, PHO12) and the corresponding proteins are increased so that the cell can better
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172
Fig. 1. Low-phosphate sensing resulting in activation of the PHO pathway. When yeast cells are starved of phosphate, the cyclin-dependent
kinase (CDK) inhibitor Pho81 inactivates the Pho80–Pho85 complex. The
transcription factor Pho4 is unphosphorylated and active, leading to the
induction of PHO genes to scavenge phosphate from the environment.
scavenge phosphate from the surroundings (Lenburg &
O’Shea, 1996; Oshima, 1997). High-capacity uptake of free
phosphate from outside the cell under phosphate-limited
growth conditions is mediated by the H1-coupled Pho84
cotransporter (Bun-ya et al., 1991). Expression of PHO84 is
derepressed when the external phosphate concentration of
the growth medium decreases to about 100 mM (Petersson
et al., 1999; Lagerstedt et al., 2002). A metabolic signal from
inside the cell, regulating the phosphate homeostasis and the
phosphate starvation responses, has been proposed (Wykoff
& O’Shea, 2001; Auesukaree et al., 2004). Indeed, the
disruption of PHO84 results in the constitutive expression
of PHO5 (Bun-ya et al., 1991), suggesting that a defect in
phosphate uptake in the Dpho84 strain may lead to a lower
level of intracellular phosphate that mimics the effects of
phosphate starvation and thereby serves as a signal for the
PHO pathway. Moreover, the levels of intracellular Pi and
polyphosphate (polyP) strongly influence the regulation of
the expression of PHO5, the main secreted acid phosphatase
(Auesukaree et al., 2004). As an additional survival strategy,
polyP is synthesized and accumulated mainly in the vacuole
and represents a Pi reserve used during periods of Pi
starvation (Kulaev, 1979; Kulaev & Vagabov, 1983; Kulaev &
Kulakovskaya, 2000). Upon transfer of cells to a Pi-deficient
medium, a rapid decrease of polyP content is seen in whole
cells and vacuoles (Kulaev et al., 1999). This mobilization of
stored Pi is accomplished by the concerted action of several
different phosphatases (Oshima, 1997). Furthermore, a
lowered capacity to synthesize polyP exerts control on the
rate at which Pi is taken up, possibly via a transient increase
in the level of Pi in the cytosol. The polyP thus plays a
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J.-M. Mouillon & B.L. Persson
significant role in increasing the cell’s endurance to unfavourable environmental conditions and in regulating biochemical processes. The internal reserves of Pi and polyP are
apparently metabolized prior to the sensing of a reduced
availability of external phosphate, suggesting that the disappearance of polyP is due to a short-term response to
phosphate starvation (Pratt et al., 2004). The polyP pool
also acts as a buffer that can be mobilized during periods of
Pi limitation and enables the phosphate-responsive signalling pathway to filter transient fluctuations in extracellular
Pi levels (Thomas & O’Shea, 2005). Recently, additional
factors such as diphosphoinositol tetrabisphosphate and/or
bis-diphosphoinositol triphosphate have been proposed to
be involved in phosphate regulation, independently of the
intracellular Pi level (Auesukaree et al., 2005). All these
findings strongly suggest that an intracellular phosphate
sensing occurs to initiate the PHO pathway when cells are
shifted from high-Pi to low-Pi growth conditions (Fig. 1),
but the intracellular phosphate sensor at the molecular level
has yet to be identified.
A rapid phosphate signalling is
responsible for Pho84 degradation
Synthesis and transport activity of Pho84 is maintained at its
highest levels at a cell density corresponding to midexponential growth phase during logarithmic low-Pi batch
growth, a condition at which the extracellular phosphate
concentration is in the range 30–40 mM. At lower phosphate
concentrations the protein is removed from the plasma
membrane and is subjected to vacuolar sorting and degradation (Lagerstedt et al., 2002; Persson et al., 2003). An
enhanced degradation of the Pho84 transporter is also
observed within 60 min when repressive amounts of phosphate (10 mM) are added to low-Pi-grown cells (Fig. 2;
Lagerstedt et al., 2002; Pratt et al., 2004). Removal of the
Pho84 transporter in response to external Pi elevation
occurs in a concentration-dependent manner with respect
to Pi, as evidenced by the fact that lower concentrations of
added Pi (0.1 and 1 mM) do not affect the stability of the
transporter (Pratt et al., 2004). Down-regulation and degradation of Pho84 are also triggered by the use of the
nonmetabolized phosphate analogue methylphosphonate
(MP), when added at a concentration of 10 mM to low-Pigrown cells (Pratt et al., 2004). MP appears to be recognized
as a Pho84 substrate and to convey a true phosphate-like
response at the level of Pho84 protein expression and
degradation. The usefulness of MP to dissect the phosphate
signalling and expression of the PHO genes is further
emphasized by the fact that de-repression of the PHO84
gene is unperturbed when MP is present in the culture
media during low-phosphate growth conditions (Pratt et al.,
2004). By contrast, no major accumulation of Pho84 in the
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Phosphate sensing and signalling in Saccharomyces cerevisiae
Fig. 2. Rapid phosphate sensing from outside of the cell: activation of
protein kinase A (PKA) to convey the signal for Pho84 down-regulation
and degradation. The addition of phosphate to low-phosphate-grown
cells triggers activation of PKA through phosphate recognition by Pho84
and/or Pho87. Activation of the PKA pathway leads to an enhanced
degradation of the high-affinity phosphate transporter Pho84 in the
vacuole.
membrane is detected under these growth conditions,
suggesting a posttranscriptional regulation of Pho84 activity. Recognition of MP by Pho84 is essential to trigger Pho84
down-regulation and repression of Pho5 activity by MP, as
other phosphate transporters (Pho90, Pho91, Pho87 and
Pho89) are apparently not involved in this recognition
(Mouillon & Persson, 2005). To account for these findings,
a phosphate sensing machinery mediated by the phosphate
transporters from outside of the cell has been proposed
(Giots et al., 2003; Holsbeeks et al., 2004; Thevelein et al.,
2005). The possibility that Pho84 is active in phosphate
sensing has previously been investigated in a PHO84defective mutant where a complete de-repression of the
secreted acid phosphatase activity was observed (Wykoff &
O’Shea, 2001). However, because over-expression of the
high-affinity (Pho89) and low-affinity (Pho87, Pho90,
Pho91) inorganic phosphate transporters, or the glycerophosphoinositol transporter (Git1) in a Dpho84 strain
suppressed the constitutive phenotype, these authors ruled
out a sensing role for these transporters in the regulation of
PHO5. Indeed, the use of the phosphate analogue MP
suggests a direct molecule-sensing involving the Pho84
transporter (Pratt et al., 2004). Recently, Pho84 and Pho87
of cells starved of phosphate were also shown to be able to
sustain rapid phosphate signalling through the activation of
the PKA pathway in the presence of glucose, suggesting that
they can act as phosphate sensors by using overlapping
nutrient signal transduction pathways (Giots et al., 2003;
Thevelein et al., 2005). The phosphate signalling via PKA
FEMS Yeast Res 6 (2006) 171–176
activation is cAMP-independent and does not require the
Sch9 protein kinase (Giots et al., 2003). Activation of PKA
seems to be essential for Pho84 down-regulation and
degradation, as inhibition of PKA activity strongly alters
the removal of Pho84 from the plasma membrane in
response to external Pi elevation (Mouillon & Persson,
2005). By contrast, down-regulation of the secreted acid
phosphatases does not require activation of the PKA signalling pathway and occurs 120 min after addition of Pi to lowPi-grown cells (Mouillon & Persson, 2005). Together, these
findings suggest that Pho84 is part of the phosphate sensor
machinery involved in the cellular response to changes of
phosphate concentration in the external media (Fig. 2). The
use of plasma membrane-based nutrient sensing systems for
rapid activation of the PKA pathway has been described for
other nutrient sensing mechanisms such as for glucose,
sucrose and amino acids (Thevelein et al., 2005). These
authors suggested that the rapid activation of the PKA
pathway in nutrient-starved cells might be due to the shortterm nature of the starvation response. Stress signalling
involving both rapid and long-term responses has been
described for the AMP-activated protein kinase (AMPK)
system, which is activated by a large variety of cellular
stresses that deplete ATP. Activation of AMPK switches on
alternative catabolic pathways that generate ATP while
switching off ATP consumption via both a rapid (direct
phosphorylation of metabolic enzymes) and more longterm effects on gene and protein expression (Kahn et al.,
2005).
Long-term effects of phosphate sensing
and signalling on gene and protein
expression
Under conditions of high phosphate, the Pho80–Pho85
complex phosphorylates and inactivates the transcription
factor Pho4 by triggering the association of phosphorylated
Pho4 with the nuclear export receptor Msn5. This association leads to the rapid export of Pho4 from the nucleus to
the cytoplasm and thus to repression of PHO genes (Fig. 3).
Down-regulation of the secreted acid phosphatases does not
involve the PKA signalling pathway (Mouillon & Persson,
2005) and seems to occur via repression of the PHO pathway
when intracellular phosphate reserves have been replenished
(Auesukaree et al., 2004). Previous studies also question the
role of the high-affinity transport system in the signalling
to repress the secreted acid phosphatases (Lau et al., 1998).
These authors suggest a model to explain the constitutive
expression of secreted acid phosphatases in Dpho84 or
Dpho86 mutants, where defects in phosphate uptake might
result in a low level of intracellular Pi that serves as a signal.
Recent findings have also demonstrated a direct correlation
between intracellular Pi and polyP pools on repression of the
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Fig. 3. Internal phosphate sensing regulating repression of the PHO
pathway. Under high-phosphate conditions, the transcription factor
Pho4 is phosphorylated by the cyclin-dependent kinase complex Pho80–Pho85 and exported from the nucleus to the cytoplasm, thereby turning
off expression of the PHO genes.
secreted acid phosphatases (Auesukaree et al., 2004). Our
model also favours the idea that an intracellular Pi signal
rather than a phosphate carrier acting as a sensor is
responsible for the down-regulation of the secreted acid
phosphatases (Fig. 3). The CDK inhibitor Pho81 has been
proposed as the intracellular sensor because of its regulatory
activity in the PHO pathway and the fact that a minimal
domain of Pho81 containing 80 amino acids is both
necessary and sufficient to inhibit Pho80–Pho85 CDK
activity (Huang et al., 2001). Recently, Swinnen et al.
(2005) have shown that full-length Pho81 is also required
to control trehalose metabolism and the postdiauxic shift
stress-responsive targets. Moreover, the authors suggest that
the PHO pathway functions in parallel to the fermentable
growth medium- or Sch9-controlled pathway and that they
might share the protein kinase Rim15, which was previously
reported to play a central role in the integration of glucose,
nitrogen and amino acid availability (Roosen et al., 2004).
Several observations also indicate that activity of the
Pho80–Pho85 complex appears to be linked to the status of
other nutrients such as carbon and nitrogen, as shown by
the inability of Dpho85 cells to grow on nonfermentable
carbon sources or on media with proline as the sole nitrogen
source (Lee et al., 2000). Our model suggests that the downregulation of both the Pho84 transporter and the secreted
acid phosphatases in response to an increase in external
phosphate is a result of the two distinct pathways. Further
studies are needed to elucidate how the PHO and PKA
pathways are co-ordinated during phosphate sensing and
signalling. Interestingly, under conditions of nonlimited
carbon supply, the extracellular Pi concentration serves as a
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J.-M. Mouillon & B.L. Persson
major factor controlling expression and activity of the
Pho84 transporter (Martinez et al., 1998; Petersson et al.,
1999; Pratt et al., 2004), whereas limitation in the carbon
source results in rapid degradation of the transporter even in
the presence of de-repressing levels of Pi (Martinez et al.,
1998). The physiological regulation of Pho84 seems to
depend on the availability of both de-repressing Pi concentrations and an abundant carbon source. The presence of
glucose is also required during phosphate signalling for PKA
activation (Giots et al., 2003). The authors suggest that
glucose is in fact needed to maintain PKA in an active state,
as inactivation of both the G-protein-coupled receptor
system and the glucose-phosphorylation-dependent system
reduces the cAMP level to such an extent that PKA activity is
insufficient to sustain phosphate signalling (Giots et al.,
2003). Furthermore, rapid phosphate activation is not
prevented by complete inhibition of glycolysis, suggesting a
metabolism-independent process (Giots et al., 2003).
Whether Pho84, like many other plasma membrane proteins
in yeast, is phosphorylated and/or ubiquitinated prior to
endocytosis and vacuolar processing is so far unknown.
Primary sequence analysis of Pho84 shows that 12 lysine
residues, the target for ubiquitination, are predicted to be
cytoplasmically located, according to existing two- and
three-dimensional models (Lagerstedt et al., 2004). It remains to be seen whether these residues are functionally
important for ubiquitination/endocytosis. The Pho84 protein also contains a C-terminal sequence similar to the
amino acid sequence SINNDAKSS of the C-terminal region
of the membrane-bound Ste2 a-factor pheromone receptor,
serving as the target site for ubiquitination and phosphorylation preceding endocytosis (Hicke et al., 1998). However,
C-terminal substitution and deletion mutagenesis of both
green fluorescent protein- and C-MYC-epitope (EQKLISEEDL) tagged Pho84 proteins, followed by analysis of the
localization and function of the transporter, did not reveal
any alteration in the degradation pattern (Lagerstedt et al.,
2002). What is the physiological role of a rapid removal and
degradation of Pho84 from the plasma membrane in
response to external Pi elevation? One explanation may be
to avoid an excess uptake of Pi into the cell. Indeed, a major
uptake of Pi into the cell could have dramatic consequences
that strongly affect the electrochemical gradient across the
plasma membrane generated by H1-ATPases. Previous
studies of intact yeast cells (Bun-ya et al., 1991; Martinez
et al., 1998) and inverted plasma membrane vesicles (Fristedt et al., 1996) have shown that the Pho84 transporter
catalyses a bi-directional H1-coupled Pi uptake, where the
direction of transport is determined by the directionality of
the driving force rather than by the orientation of the
protein. Moreover, the presence of the constitutively expressed low-affinity phosphate transport system (Pho87,
Pho90 and Pho91) also allows Pi uptake when repressive
FEMS Yeast Res 6 (2006) 171–176
175
Phosphate sensing and signalling in Saccharomyces cerevisiae
amounts of Pi (10 mM) are added to low-phosphate-grown
cells and the high-affinity phosphate transport system
(Pho84, Pho89) is no longer operative.
Concluding remarks
The molecular components involved in the phosphate
sensing machinery are still unidentified but findings suggest
that phosphate sensing from both the inside and the outside
of S. cerevisiae cells occurs to adjust the phosphate response
to cellular needs. An intracellular phosphate sensing is
responsible for activation and repression of the PHO pathway and to allow the cells to respond to phosphate starvation or surplus in correlation with the cellular phosphate
reserves available. Direct phosphate molecule recognition
seems also to take place at the level of the plasma membrane,
involving the high-affinity phosphate transporter Pho84 to
adjust phosphate acquisition in response to external phosphate fluctuations. Further studies are now needed to
understand how these sensing signals are integrated and coordinated by the cell.
Acknowledgements
This work was supported by Human Frontier Science
Organization Grant RG00281/2000-M, and Swedish Research Council Grant 621-2003-3558.
References
Auesukaree C, Homma T, Tochio H, Shirakawa M, Kaneko Y &
Harashima S (2004) Intracellular phosphate serves as a signal
for the regulation of the PHO pathway in Saccharomyces
cerevisiae. J Biol Chem 279: 17289–17294.
Auesukaree C, Tochio H, Shirakawa M, Kaneko Y & Harashima S
(2005) Plc1p, Arg82p, and Kcs1p, enzymes involved in inositol
pyrophosphate synthesis, are essential for phosphate
regulation and polyphosphate accumulation in Saccharomyces
cerevisiae. J Biol Chem 280: 25127–25133.
Bun-ya M, Nishimura M, Harashima S & Oshima Y (1991) The
Pho84 gene of Saccharomyces cerevisiae encodes an inorganic
phosphate transporter. Mol Cell Biol 11: 3229–3238.
Fristedt U, Berhe A, Ensler K, Norling B & Persson BL (1996)
Isolation and characterization of membrane vesicles of
Saccharomyces cerevisiae harboring the high-affinity
phosphate transporter. Arch Biochem Biophys 330: 133–141.
Giots F, Donaton FC & Thevelein JM (2003) Inorganic phosphate
is sensed by specific phosphate carriers and acts in concert
with glucose as a nutrient signal for activation of the protein
kinase a pathway in the yeast Saccharomyces cerevisiae. Mol
Microbiol 47: 1163–1181.
Hicke L, Zanolari B & Riezman HJ (1998) Cytoplasmic tail
phosphorylation of the alpha-factor receptor is required for its
ubiquitination and internalization. J Cell Biol 141: 349–358.
FEMS Yeast Res 6 (2006) 171–176
Holsbeeks L, Lagatie O, Van Nuland A, Van de Velde S &
Thevelein JM (2004) The eukaryotic plasma membrane as a
nutrient-sensing device. Trends Biochem Sci 29: 556–564.
Huang S, Jeffery DA, Anthony MD & O’Shea EK (2001)
Functional analysis of the cyclin-dependent kinase inhibitor
Pho81 identifies a novel inhibitory domain. Mol Cell Biol 21:
6695–6705.
Kaffman A, Herskowitz I, Tjian R & O’Shea EK (1994)
Phosphorylation of the transcription factor PHO4 by a
cyclin–CDK complex, PHO80–PHO85. Science 263:
1153–1156.
Kahn BB, Alquier T, Carling D & Hardie DG (2005) AMPactivated protein kinase: ancient energy gauge provides clues
to modern understanding of metabolism. Cell Metab 1: 15–25.
Kulaev IS (1979) The Biochemistry of Inorganic Polyphosphates.
Wiley & Sons Inc, New York.
Kulaev I & Kulakovskaya T (2000) Polyphosphate and phosphate
pump. Annu Rev Microbiol 54: 709–734.
Kulaev IS & Vagabov VM (1983) Polyphosphate metabolism in
microorganisms. Adv Microb Physiol 24: 83–171.
Kulaev I, Vagabov VM & Kulakovskaya T (1999) New aspects of
polyphosphate metabolism and function. J Biosci Bioeng 88:
111–129.
Lagerstedt JO, Zvyagilskaya R, Pratt JR, Pattison-Granberg J,
Kruckeberg AL, Berden JA & Persson BL (2002) Mutagenic
and functional analysis of the C-terminus of Saccharomyces
cerevisiae Pho84 phosphate transporter. FEBS Lett 526: 31–37.
Lagerstedt JO, Voss JC, Wieslander A & Persson BL (2004)
Structural modeling of dual-affinity purified Pho84 phosphate
transporter. FEBS Lett 578: 262–268.
Lau WT, Schneider KR & O’Shea EK (1998) A genetic study of
signaling processes for repression of PHO5 transcription in
Saccharomyces cerevisiae. Genetics 150: 1349–1359.
Lee M, O’Regan S, Moreau JL, Johnson AL, Johnston LH &
Goding CR (2000) Regulation of the Pcl7–Pho85 cyclin–cdk
complex by Pho81. Mol Microbiol 38: 411–422.
Lenburg ME & O’Shea EK (1996) Signaling phosphate starvation.
Trends Biochem Sci 21: 383–387.
Martinez P, Zvyagilskaya R, Allard P & Person BL (1998)
Physiological regulation of the derepressive phosphate
transport in Saccharomyces cerevisiae. J Bacteriol 180:
2253–2256.
Mouillon JM & Persson BL (2005) Inhibition of the protein
kinase A alters the degradation of the high-affinity phosphate
transporter Pho84 in Saccharomyces cerevisiae. Curr Genet 48:
226–234.
Oshima Y (1997) The phosphatase system in Saccharomyces
cerevisiae. Genes Genet Syst 72: 323–334.
Persson BL, Lagerstedt JO, Pratt JR, Pattison-Granberg J, Lundh
K, Shokrollahzadeh S & Lundh F (2003) Regulation of
phosphate acquisition in Saccharomyces cerevisiae. Curr Genet
43: 225–244.
Petersson J, Pattison J, Kruckeberg AL, Berden JA & Persson BL
(1999) Intracellular localization of an active green fluorescent
2006 Federation of European Microbiological Societies
Published by Blackwell Publishing Ltd. All rights reserved
c
176
protein-tagged Pho84 phosphate permease in Saccharomyces
cerevisiae. FEBS Lett 462: 37–42.
Pratt JR, Mouillon JM, Lagerstedt JO, Pattison-Granberg J,
Lundh KI & Persson BL (2004) Effects of methylphosphonate,
a phosphate analogue, on the expression and degradation of
the high-affinity phosphate transporter Pho84, in
Saccharomyces cerevisiae. Biochemistry 43: 14444–14453.
Roosen J, Oesterhelt C, Pardons K, Swinnen E & Winderickx J
(2004) Integration of nutrient signalling pathways in the yeast
Saccharomyces cerevisiae. Nutrient-Induced Responses in
Eukaryotic Cells. (Winderickx J & Taylor PM, eds), pp.
277–318. Topics in Current Genetics. Springer, Berlin.
Swinnen E, Rosseels J & Winderickx J (2005) The minimum
domain of Pho81 is not sufficient to control the Pho85–Rim15
effector branch involved in phosphate starvation-induced
stress responses. Curr Genet 48: 18–33.
2006 Federation of European Microbiological Societies
Published by Blackwell Publishing Ltd. All rights reserved
c
J.-M. Mouillon & B.L. Persson
Thevelein JM, Geladé R, Holsbeeks I, et al. (2005) Nutrient
sensing systems for rapid activation of the protein kinase A
pathway in yeast. Biochem Soc Trans 33: 253–256.
Thomas MR & O’Shea EK (2005) An intracellular phosphate
buffer filters transient fluctuations in extracellular
phosphate levels. Proc Natl Acad Sci USA 102:
9565–9570.
Toh-e A, Tanaka K, Uesono Y & Wickner RB (1988) PHO85, a
negative regulator of the PHO system, is a homolog of the
protein kinase gene CDC28, of Saccharomyces cerevisiae. Mol
Gen Genet 214: 162–164.
Vogel K, Horz W & Hinnen A (1989) The two positively acting
regulatory proteins PHO2 and PHO4 physically interact with
PHO5 upstream activation regions. Mol Cell Biol 9:
2050–2057.
Wykoff DD & O’Shea EK (2001) Phosphate transport and sensing
in Saccharomyces cerevisiae. Genetics 159: 1491–1499.
FEMS Yeast Res 6 (2006) 171–176