| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
|
Plant Physiol. (1998) 117: 723-731 UPDATE ON SIGNAL TRANSDUCTION
The Two-Component System1
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
 |
SENSORY-RESPONSE CIRCUITS: REALITY CHECKS AT THE CELLULAR LEVEL |
|---|
Top
References
|
|---|
Unicellular microorganisms
experience "life on the edge," as they have little ability to
change their environment and face fierce competition for limited
resources. They must therefore respond to a barrage of environmental
cues in a rapid and accurate manner. Among multicellular organisms,
plants in particular cannot escape their environment and so must be
masters at adapting and coordinating cellular events to accommodate
prevailing conditions. The penalty for losing touch with reality is
often death. The study of sensory-response systems has defined the
basics of how many organisms detect and respond with exquisite
sensitivity to changes in their chemical or physical environments. Such
studies have recently focused on events that occur at the cellular and molecular levels, elucidating the mechanisms of detecting extracellular signals and transducing such signals into the appropriate intracellular events. In a large number of cases, these signaling pathways involve phosphorylation of key effector proteins by protein kinases. In bacteria numerous sensory-response circuits operate by making use of a
phosphorylation control mechanism referred to as the "two-component
system" (Nixon et al., 1986
; Parkinson and Kofoid, 1992).
for the NR system, a
regulatory system that controls gene expression in response to
nitrogen-source availability in Escherichia coli. At
about the same time, Ausubel and co-workers (Nixon et al., 1986)
recognized amino acid sequence similarities between the components of
the NR system and components of numerous other bacterial sensory
systems that had not been characterized at a biochemical level. Such
similarities raised the exciting possibility that these other systems
operated via a signaling mechanism analogous to that utilized by the NR
system. Subsequent work has borne out this idea, and the list of
two-component systems has expanded to include hundreds of distinct
systems. Fueled in part by the explosion of sequence information
provided by various genome projects, the number of two-component
systems continues to grow at a rapid pace, and numerous review articles
on the topic have been published (e.g. Stock et al., 1990; Bourret et
al., 1991; Parkinson and Kofoid, 1992; Hoch and Silhavy, 1995).
;
Wurgler-Murphy et al., 1997). In the first part of this
review, we outline the basics of how two-component systems operate in
well-characterized bacterial systems. In the second part, we review the
emerging picture of two-component signaling in the context of
eukaryotic cells, particularly in higher plants.
| |
BASIC PLAYERS: IT TAKES TWO TO SIGNAL |
|---|
The basic two-component system involves a sensor kinase, or HPK, as well as an RR. As depicted in Figure 1, the role of the HPK is to direct phosphorylation of its cognate RR in response to a specific environmental signal; this phosphorylation regulates the activity of the RR. Some bacteria make extensive use of such systems. For example, inspection of the complete genome of E. coli indicates that over 30 distinct HPK-RR circuits operate in this single bacterium. Basic Local Alignment Search Tool (BLAST) searches of the Mycoplasma genetilium genome database, however, revealed no likely HPK homologs, suggesting that not all prokaryotes utilize two-component systems as extensively as E. coli. Similar surveys of other sequence databases indicate that while some eukaryotes (e.g. Arabidopsis thaliana) may have a number of two-component systems, others (e.g. Saccharomyces cerevisiae) appear to have only a single two-component system. Here we outline some of the basic characteristics common to the large families of two-component HPKs and RRs.
|
Sensor HPKs
In several respects, HPKs are similar to the well-defined family of receptor Tyr kinases (Stock et al., 1991): HPKs operate as dimers
and autophosphorylate; they are associated with the cytoplasmic
membrane, usually via one or two membrane-spanning sequences; and they
typically contain extracellular sensory input modules fused to the
protein kinase catalytic module (Bourret et al., 1991). This
arrangement makes it easy to envision environmental stimuli impinging
on the HPK in a manner that regulates its kinase activity. However,
there are relatively few cases in which we have much understanding of
the actual ligands that interact directly with the HPKs, and in several
cases a distinct protein serves as the primary receptor for the
stimulus (Fig. 2, A and B). Because of
this, it has been difficult to determine the exact relationship between
signal perception and catalytic activity of the HPK (e.g. whether the
signal stimulates HPK activity). Despite the general mechanistic
similarities shared by HPKs and other types of protein kinases,
sequence analysis indicates that HPKs are only distantly related to Tyr
kinases and Ser/Thr kinases (Stock et al., 1995).
|
). The
energetics and chemical stabilities of phospho-His and phospho-Asp differ significantly from those of "more traditional" phospho-amino acids (phospho-Tyr, phospho-Ser, and phospho-Thr) (Stock et al., 1990,
1995).
; Stock et al., 1995). Some HPKs
also have phosphatase activities, i.e. they can catalyze
dephosphorylation of their cognate RRs (Igo et al., 1989; Makino et
al., 1989). This dephosphorylation appears to involve a mechanism that
is distinct from simple reversal of the HPK-RR phosphotransfer reaction
(Hsing and Silhavy, 1997).
RRs
The sensor HPK regulates the activity of a cytoplasmic RR by directing its phosphorylation as depicted in Figure 1. GenBank now contains over 400 different examples of RRs. Analysis of the amino acid sequences of known and suspected RRs has established two general themes: (a) RRs have an approximately 110-amino acid domain referred to as a "receiver module" that contains the Asp-phosphorylation site; and (b) most RRs are two-domain proteins in which the receiver module is fused to a second domain having some kind of output or effector activity (Parkinson and Kofoid, 1992). In many cases, the
output domain is a DNA-binding module whereby the RR functions as a
transcription factor, and Asp phosphorylation serves to control its
ability to either bind its target DNA sequence or interact with other
components of the transcription machinery (Hakenbeck and Stock, 1996).
). In the case of
E. coli SprE, the output module regulates the activity of a
protease (Pratt and Silhavy, 1996). Thus, the basic conformational changes associated with receiver phosphorylation are able to
control a variety of activities (Lowry et al., 1994). If one excludes sequences of closely related homologs (e.g. NRI
from two closely related bacterial species), receiver modules from any
two RRs share sequence identity at only 20 to 30% of the positions,
but all receiver modules are thought to have a similar
three-dimensional structure (Stock et al., 1990; Volz, 1993). X-ray
crystal structures and/or NMR-derived three-dimensional structures have
been obtained for CheY (Stock et al., 1989; Volz and Matsumura, 1991),
Spo0F (Feher et al., 1997), and NarL (Baikalov et al., 1996) proteins. These structures indicate a common 
protein structure for the receiver modules in RRs, with the phosphorylation site located in the
loop connecting two of the central strands of sheet that comprise
the core of the receiver module structure. The three-dimensional structures of receiver modules are strikingly similar to that of the
small GTP-binding protein Ras (Stock et al., 1991). This similarity is
especially interesting in view of the ability of Ras to control MAPK
pathways in several eukaryotic systems as we discuss later (Avruch et
al., 1994).
A "Simple" Example
The EnvZ-OmpR system of E. coli provides a relatively straightforward example of the basics of two-component signaling (Fig. 1). This system regulates the expression of the ompF and ompC porin genes in response to changes in extracellular osmolarity (Pratt and Silhavy, 1995). EnvZ is an autophosphorylating
HPK that serves as an osmosensor. The osmo-sensing module of EnvZ is
located in the periplasmic space of the bacterial cell, and the EnvZ
transmitter domain is situated in the cytoplasm. The actual signal
perceived by EnvZ has not been determined, but under conditions of high
osmolarity, autophosphorylated EnvZ readily transfers its high-energy
His-phosphoryl group to the conserved Asp in the receiver module of the
RR OmpR. P-OmpR binds to sequences upstream of the ompF and
ompC genes, regulating their expression.
).
| |
LESSONS LEARNED FROM BACTERIAL TWO-COMPONENT SYSTEMS |
|---|
Modularity
Because RRs and HPKs are modular, it has been possible to determine the activities of isolated domains of these proteins. For example, in vitro studies on HPK activity have often been carried out on modified versions of HPKs that lack membrane-associated regions. In many cases (including that of EnvZ), deletion of such regions removes the sensory-input modules, resulting in a partially or completely active form of the kinase (Parkinson and Kofoid, 1992). This indicates
that the input domain may often serve to inhibit kinase activity, and
suggests that a common mechanism of kinase regulation could be the
removal of this inhibition. Without knowing the ligands or "direct
stimuli" for most HPKs, however, it is difficult to test these ideas.
An added complication in such analyses is that the input domain may
simultaneously regulate phosphatase activity of the HPK.
; Kahn and Ditta, 1991;
Baikolov et al., 1996), and those in which it operates in a positive
manner to stimulate RR output (Drummond et al., 1990; Tsuzuki et al.,
1994).
More-than-Two-Component Systems
Although some two-component systems appear to be as simple as indicated in Figure 1, many systems are more complex and involve either additional two-component modules or a variety of accessory proteins (e.g. Fig. 2). Some two-component systems, for instance, require an additional phosphatase to control the phosphorylation level of the RR. There are also numerous examples of systems that utilize more than one HPK or RR. These examples include: (a) multiple HPKs directing a single RR, (b) multiple RRs directed by a single HPK, (c) multistep phosphotransfer relays, and (d) hybrid sensor HPKs (Parkinson and Kofoid, 1992). Many of the sensor kinases identified in eukaryotic
systems are hybrid HPKs, in which a receiver module is fused to the HPK
such that a single protein encompasses both of the two-component
elements. Most hybrid kinases appear to phosphorylate a receiver module
on a second distinct protein; this opens up the possibility of having
different pathways by which a phosphate can be transferred from a
His-phosphorylation site to a receiver module (Appleby et al., 1996).
FrzE in Myxococcus xanthus provides an interesting exception
to this generality in that this hybrid kinase appears to be capable of
carrying out effector functions without the help of a distinct RR (Ward
and Zusman, 1997).
Control Points
Different two-component systems appear to control RR phosphorylation levels via somewhat distinct mechanisms. For example, in response to a stimulus some systems alter RR-phosphorylation levels by controlling the rate of HPK autophosphorylation (Borkovich and Simon, 1990), whereas in other systems it is the phosphatase activity
of the HPK or an additional component that is regulated in response to
a stimulus (Atkinson et al., 1994; Perego and Hoch, 1996). This
diversity underscores the impressive flexibility of two-component
circuitry; it can be modified to operate in a variety of different
contexts using different aspects of the basic protein structures of
receiver and transmitter modules and the basic biochemistry of the
phosphorylation/dephosphorylation chemistry.
Science by Analogy: Proceed with Caution
Several HPK-RR pairs have been subjected to extensive random and site-directed mutagenesis. The resulting mutants have helped to define functionally important positions within the respective transmitter and receiver modules of each HPK-RR pair. It seems reasonable to expect that such positions identified in one system would also play important roles in other two-component systems, and that mutations at such sites could be useful starting points for analyzing newly discovered two-component systems. In practice, however, such an approach has not been very successful. For mutation sites that are outside of the immediate vicinity of the active sites of HPKs and RRs, there are numerous examples of mutations that have a strong phenotype in one system but not in another (Parkinson and Kofoid, 1992; Stock et al.,
1995). Results obtained with the HPK homolog SpoIIAB in Bacillus
subtilis further underscore the need for caution when using
sequence homology information to make predictions about function or
mechanism: SpoIIAB actually operates as a Ser protein kinase,
phosphorylating another protein (SpoIIAA) without any involvement of
the His-Asp phosphorelay that is the hallmark of traditional
two-component systems (Min et al., 1993).
| |
EUKARYOTIC TWO-COMPONENT SYSTEMS |
|---|
Members of the two-component family are now starting to be found
with increasing frequency in eukaryotes, suggesting that the basic
His-to-Asp phosphotransfer mechanism is employed by a variety of
eukaryotic sensory-response pathways (Loomis et al., 1997;
Wurgler-Murphy and Saito, 1997). A number of genes encoding HPKs,
hybrid HPKs, and RRs have been reported in yeasts (S. cerevisiae, Schizosaccharomyces pombe, and
Candida albicans), in the slime mold Dictyostelium
discoideum, in Neurospora crassa, and in higher plants
(e.g. Brown et al., 1993; Chang et al., 1993; Ota and Varshavsky, 1993;
Wilkinson et al., 1995; Alex et al., 1996; Kakimoto, 1996; Posas et
al., 1996; Schuster et al., 1996; Shaulsky et al., 1996; Wang et al.,
1996; Sakakibara et al., 1998).
).
Receptors for Ethylene
), in the budding yeast S. cerevisiae (Posas et al.,
1996), in the fission yeast S. pombe (Shieh et al., 1997),
and in the slime mold D. discoideum (Schuster et al., 1996).
In addition, an HPK in D. discoideum regulates gene
expression in prestalk cells and controls terminal differentiation of
prespore cells (Wang et al., 1996) in a manner that generally resembles
the two-component pathway controlling sporulation in the bacterium
B. subtilis (Hoch, 1995). Fourth, several eukaryotic
two-component systems appear to regulate extended downstream effector
cascades; that is, the two-component system may comprise only the
upstream portion of a more extensive signaling pathway. This situation
represents a clear difference from most prokaryotic two-component
systems, in which the HPK-RR circuit comprises most or all of the
sensory-response pathway, with the RR components serving as the
end-of-the-line effectors. Several eukaryotic two-component pathways,
including their output activities, are outlined in Table
I.
View this table:
Table I.
Some of the known eukaryotic two-component systems
and their output activities
TWO-COMPONENT REGULATORS IN HIGHER PLANTS
; Hua et al., 1995, 1997;
Schaller and Bleecker, 1995). Their predicted protein sequences are
most similar to one another in the amino-terminal "sensory input"
module (67-82% amino acid similarity). For ETR1, this region was
shown to bind ethylene in a reversible and saturable manner, providing
compelling evidence that ETR1 is an ethylene receptor (Schaller and
Bleecker, 1995). It seems likely that ERS, ETR2, and EIN4 will also be
found to bind ethylene, based on their sequence similarities with ETR1 as well as their similar ethylene-insensitive mutant phenotypes. The
carboxyl-terminal portion of each of these ethylene receptors contains
a putative HPK transmitter module. ETR1, ETR2, and EIN4 also have a
carboxyl-terminal receiver module fused to the transmitter. Thus, ETR1,
ETR2, and EIN4 have adopted the hybrid HPK arrangement, whereas ERS has
the appearance of a typical HPK. The ETR2 sequence is the most diverged
from the bacterial HPK consensus sequences, lacking, for example, the
conserved His autophosphorylation site (Hua et al., 1997). Although RRs
would be the predicted effectors for the ethylene receptors, there is
currently no evidence that RRs function in ethylene signal
transduction.
). It is unclear why plants have
multiple receptors for ethylene. Conceivably, the different receptors
have tissue- or stage-specific functions (partially redundant) or act
together as a hetero-multimeric receptor complex. A similar family of
two-component ethylene receptors exists in tomato (Wilkinson et al.,
1995; Yen et al., 1995; Zhou et al., 1996), and one of these homologs
was identified as the gene for Never-Ripe (Wilkinson et al.,
1995). Never-Ripe mutants have a dominant
ethylene-insensitive phenotype, which includes a severe delay in fruit
ripening (Yen et al., 1995).
Cytokinin Signaling
Recently, another two-component gene, CKI1, was identified in Arabidopsis. The CKI1 gene was isolated from an enhancer-tagged line on the basis of cytokinin-independent hypocotyl growth (Kakimoto, 1996). This particular phenotype suggests that a
two-component system might be involved in cytokinin signal
transduction. CKI1 encodes a hybrid HPK comprised of a
unique amino-terminal domain followed by a transmitter domain and a
receiver domain. The amino-terminal portion of CKI1 (the presumed
sensory-input module) has no sequence similarity to that of the
ethylene-receptor family, and one attractive hypothesis is that CKI1
serves as a receptor for cytokinin. In maize there is an RR gene that
might be involved in cytokinin-mediated nitrogen signaling from root to
shoot; expression of this RR gene was induced by nanomolar
concentrations of t-zeatin in detached maize leaves (Sakakibara et al.,
1998).
Clues to Plant Phytochrome Action
The mechanism of plant phytochrome signaling has long remained elusive. One suggested mechanism is Ser protein kinase activity, but this has not been firmly established (Quail, 1997). In 1991, Schneider-Poetsch noted limited but discernable sequence similarity (roughly 25% identity) between bacterial HPKs and the
carboxyl-terminal portion of plant phytochromes, leading to the
proposal that phytochrome action might involve a two-component
mechanism (Schneider-Poetsch et al., 1991). Currently, there is no
evidence that plant phytochromes possess such activity; however, recent
work in cyanobacteria strongly suggests that higher plant phytochromes
are at least derived from an ancestral HPK-RR system. The strongest
evidence comes from studies on the cyanobacterial Synechocystis
cph1 gene, which codes for a spectrally functional phytochrome
(the only such protein currently known in prokaryotes) (Hughes et al.,
1997; Yeh et al., 1997).
). The amino-terminal domain of Cph1 has sequence similarity to plant phytochromes and is capable of binding chromophores and of undergoing red/far-red light-induced reversible absorbance changes (Hughes et al.,
1997; Yeh et al., 1997). Moreover, the phosphate on Cph1 is transferred
from the His to an Asp residue in the separate RR Rcp1 (Yeh et al.,
1997). Cph1 and Rcp1 thus form a light-regulated two-component system,
which has implications for the activity of phytochromes in higher
plants. His autokinase activity is exhibited by the Pr form of Cph1
rather than by the Pfr form, even though Pfr is normally thought of as
the light-activated form; this suggests that the dark (Pr) form is the
active form of phytochrome and that red light reduces or shuts off its
activity.
). RcaC is a response regulator that might act downstream of RcaE in regulating light responses in F. diplosiphon
(Kehoe and Grossman, 1996).
| |
DIVERSITY IN SIGNALING OUTPUT |
|---|
As we have discussed, in most prokaryotic two-component systems, a
membrane-associated HPK directs the activity of an RR that functions as
a transcription factor. Thus, the typical output of the prokaryotic
HPK-RR circuit is direct control of gene expression. What about the
immediate output activity of two-component systems in eukaryotes? So
far, only S. cerevisiae RR Skn7 appears to fit the
"classic" prokaryotic model, operating as a transcription factor
(Brown et al., 1994). However, even with Skn7 there are indications of
intriguing complexities such as regulation by multiple sensory inputs
(Brown et al., 1994; Page et al., 1996) and involvement in a diversity
of processes ranging from cell wall biosynthesis (Brown et al., 1993)
to oxidative stress responses (Krems et al., 1996; Morgan et al., 1997)
and even G1 cyclin expression (Morgan et al., 1995). None of the other
known eukaryotic RRs resembles a transcription factor, and none of the
known eukaryotic HPK proteins appears to contain an output module.
Based on the few available examples (described below), the trend in
eukaryotes is that the immediate/direct output activities of
two-component systems lie farther upstream of the ultimate regulators
of gene expression (Table I).
MAPK Cascades
In three different pathways, the identification of downstream signaling elements has revealed coupling of the two-component system with the distinctly eukaryotic MAPK cascade. This is a new twist on the two-component system, as bacteria are not known to contain MAPK cascades. This also represents a new type of regulation of these cascades, which are more typically known to be regulated by upstream Tyr kinase receptors or seven-transmembrane (G-protein-coupled) receptors (Blumer and Johnson, 1994). The most established example of
two-component regulation of a MAPK cascade is the S. cerevisiae osmolarity-response pathway, which controls adaptive
responses to high osmolarity. The pathway involves a multistep
phosphorelay from His to Asp to His to Asp residues (Posas et al.,
1996). This multistep phosphorelay system can be found with slight
variations in several bacterial two-component pathways such as that
shown in Figure 2C (Appleby et al., 1996).
). Similar to the
Synechocystis Cph1 phytochrome, SLN1 has His autokinase
activity in the absence of the apparent signal (high osmolarity),
suggesting that the SLN1 HPK is inactivated by the signal. In the next
step of the phosphorelay, the phosphate is transferred from the His to
an Asp in the SLN1 receiver module. The phosphate is then transferred to a His residue on a small intermediary protein called YPD1, and
finally the phosphate is transferred to an Asp residue on a separate RR
called SSK1 (Posas et al., 1996). Such an elaboration on the basic
two-component system may allow for additional regulation, including the
integration of different signals.
, 1995). Under low-osmolarity conditions, the
phosphorylation described above renders SSK1 inactive; under high-osmolarity conditions, SSK1 is unphosphorylated and activates two
redundant MAPKKKs, SSK2 and SSK22. SSK1 is known to physically interact
with the regulatory domains of both of these MAPKKKs, although the
mechanism of stimulation is unclear. Next, SSK2 and SSK22 activate the
MAPKK PBS2, which in turn activates the MAPK HOG1. The action of this
MAPK pathway results in the expression of GPD1, which
encodes a key enzyme in glycerol biosynthesis, leading to adaptive
responses to high osmolarity (Wurgler-Murphy and Saito, 1997).
). Msc4 and Wak1 are structurally and functionally homologous to the SSK1 RR and the SSK2/SSK22 MAPKKKs, respectively. These parallels with the S. cerevisiae
osmolarity-response pathway suggest that there may be one or more
two-component sensors controlling the S. pombe pathway. In
addition to this stress-activated pathway, Mcs4 controls the timing of
mitotic initiation via an StyI-independent pathway that has
yet to be defined (Shieh et al., 1997).
). Thus, it is likely that the ethylene-response pathway contains a MAPK cascade controlled by the
two-component ethylene receptors. So far, a MAPKK and MAPK for this
pathway have not been conclusively identified. There is evidence that
the putative regulatory domain of CTR1 can physically associate with
the transmitter domains of ETR1 and ERS, as well as with the receiver
domain of ETR1, raising the possibility that the regulation of CTR1
activity involves direct interaction of CTR1 with the receptors (Clark
et al., 1998). It remains to be seen whether the receptors provide
direct "output" to CTR1 or whether additional two-component
proteins such as RRs are involved. However, in view of the remarkable
adaptability of the basic two-component elements, it would not be
surprising if ethylene signal transduction reveals yet another
variation on two-component signaling pathways.
Other Pathways
Given the above examples of MAPK regulation by eukaryotic two-component systems, it is important to point out that this is not always the case and may not even be a common situation. Other familiar eukaryotic signaling cascades may also be regulated by two-component systems. For example, the DhkA-RegA two-component system in the slime mold D. discoideum regulates cAMP phosphodiesterase activity of RR RegA (Shaulsky et al., 1998). Adjustments of cAMP levels via
DhkA-RegA are responsible for controlling the activity of a
cAMP-dependent protein kinase, which plays a key role in controlling
the complex morphogenetic events that result in sporulation (Shaulsky
et al., 1996, 1998). Another two-component system that points to
diversity in signaling output is the osmotic-response system of
D. discoideum. In this system, the hybrid HPK DokA may regulate events that are quite different from those described above for
the yeast osmosensor SLN1. This slime mold does not appear to cope with
conditions of high osmolarity by accumulating compatible osmolytes such
as glycerol, but by events involving the cytoskeleton (Schuster et al.,
1996). The pathway linking DokA to such events remains to be
determined, but may provide yet another example of the diversity of
signaling output regulated by two-component systems in eukaryotes.
| |
SUMMARY |
|---|
The basic two-component system involves two large families of signaling modules that build upon a His-to-Asp phosphotransfer theme. Bacteria display numerous variations on this theme, illustrating the flexibility of the system. There is growing evidence, including a number of unpublished reports, that two-component regulators and distant relatives play important sensory-response roles in eukaryotes. These eukaryotic systems reveal further diversification of the two-component-based circuitry, most notably in the regulation of MAPK modules. Although quite a lot has been learned about how two-component systems operate, there remain numerous fundamental questions in both eukaryotic and prokaryotic systems; for example: How is HPK activity regulated by sensory input? What is the nature of the structural change resulting from receiver module phosphorylation, and how does this change result in the activation/deactivation of output activity? Are there "one-component" systems in which an "orphan" receiver module or transmitter module operates without a partner? In cells containing multiple two-component systems that respond to different stimuli, how is specificity maintained so as to minimize inappropriate "cross-talk"? Are there examples of two-component systems in which the transmitter and receiver modules direct protein-protein interactions but do not involve protein phosphorylation? As more and more two-component systems are discovered, and as the number of researchers in this field grows, we look forward to the resolution of these issues, as well as to further surprises from these versatile signaling modules.
| |
FOOTNOTES |
|---|
Received February 23, 1998;
accepted March 6, 1998.
| |
ABBREVIATIONS |
|---|
Abbreviations: HPK, His protein kinase. MAP, mitogen-activated protein. MAPK, MAP kinase. NR, nitrogen regulatory protein. RR, response-regulator protein.
| |
LITERATURE CITED |
|---|
Top
References
|
|---|
Alex LA,
Borkovich KA,
Simon MI
(1996)
Hyphal development in Neurospora crassa: involvement of a two-component histidine kinase.
Proc Natl Acad Sci USA
93:
3416-3421
Appleby JL, Parkinson JS, Bourret RB (1996) Signal transduction via the multi-step phosphorelay: not necessarily a road less traveled. Cell 86: 845-848[CrossRef][ISI][Medline]
Avruch J, Zhang X-F, Kyriakis JM (1994) Raf meets Ras: completing the framework of a signal transduction pathway. Trends Biochem Sci 19: 279-283[CrossRef][ISI][Medline]
Baikalov I, Schroder I, Kaczor-Grzeskowiak M, Gresckowiak K, Gunsalus RP, Dickerson RE (1996) Structure of the Escherichia coli response regulator NarL. Biochemistry 35: 11053-11061[CrossRef][Medline]
Blumer KJ, Johnson GL (1994) Diversity in function and regulation of MAP kinase pathways. Trends Biochem Sci 19: 236-240[CrossRef][ISI][Medline]
Borkovich KA, Simon MI (1990) The dynamics of protein phosphorylation in bacterial chemotaxis. Cell 63: 1339-1348[CrossRef][ISI][Medline]
Bourret RB, Borkovich KA, Simon MI (1991) Signal transduction pathways involving protein phosphorylation in prokaryotes. Annu Rev Biochem 60: 401-441[CrossRef][ISI][Medline]
Brown JL, Bussey H, Stewart RC (1994) Yeast Skn7p functions in a eukaryotic two-component regulatory pathway. EMBO J 13: 5186-5194[ISI][Medline]
Brown JL,
North S,
Bussey H
(1993)
SKN7, a yeast multicopy suppressor of a mutation affecting cell wall -glucan assembly, encodes a product with domains homologous to prokaryotic two-component regulators and to heat shock transcription factors.
J Bacteriol
175:
6908-6915
Chang C,
Kwok SF,
Bleecker AB,
Meyerowitz EM
(1993)
Arabidopsis ethylene-response gene ETR1: similarity of product to two-component regulators.
Science
262:
539-544
Clark KL,
Larsen PB,
Wang X,
Chang C
(1998)
Association of the Arabidopsis CTR1 Raf-like kinase with the ETR1 and ERS ethylene receptors.
Proc Natl Acad Sci USA
95:
5401-5406
Drummond MH, Contreras A, Mitchenall LA (1990) Mol Microbiol 4: 29-37[CrossRef][ISI][Medline]
Feher VA, Zapf JW, Hoch JA, Whiteley JM, McIntosh LP, Rance M, Skelton NJ, Dahlquist FW, Cavanagh J (1997) High-resolution NMR structure and backbone dynamics of the Bacillus subtilis response regulator, Spo0F: implications for phosphorylation and molecular recognition. Biochemistry 36: 10015-25[CrossRef][Medline]
Hakenbeck R, Stock JB (1996) Analysis of two-component signal transduction systems involved in transcriptional regulation. Methods Enzymol 273: 281-300[ISI][Medline]
Hoch JA (1995) Control of cellular development in sporulating bacteria by the phosphorelay two-component signal transduction system. In J Hoch, T Silhavy, eds, Two-Component Signal Transduction. ASM Press, Washington, DC, pp 129-144
Hoch JA, Silhavy TJ (1995) Two-Component Signal Transduction. ASM Press, Washington, DC
Hsing W,
Silhavy TJ
(1997)
Function of conserved histidine-243 in phosphatase activity of EnvZ, the sensor for porin osmoregulation in Escherichia coli.
J Bacteriol
179:
3729-3735
Hua J,
Chang C,
Sun Q,
Meyerowitz EM
(1995)
Ethylene insensitivity conferred by Arabidopsis ERS gene.
Science
269:
1712-1714
Hua J, Sakai H, Meyerowitz EM (1997) The ethylene receptor gene family in Arabidopsis. In AK Kanellis, C Chang, H Kende, D Grierson, eds, Biology and Biotechnology of the Plant Hormone Ethylene. Kluwer Academic Publishers, Dordrecht, The Netherlands, pp 71-76
Hughes J, Lamparter T, Mittman F, Hartmann E, Gärtner W, Wilde A, Börner T (1997) A prokaryotic phytochrome. Nature 386: 663[CrossRef][Medline]
Igo M,
Ninfa AJ,
Stock JB,
Silhavy TJ
(1989)
Phosphorylation and dephosphorylation of a bacterial transcriptional activator by a transmembrane receptor.
Genes Dev
3:
1725-1734
Kahn D,
Ditta G
(1991)
Modular structure of FixJ: homology of the transcriptional activator domain with the 
35 binding domain of sigma factors.
Mol Microbiol
5:
987-997[CrossRef][Medline]
Kakimoto T
(1996)
CKI1, a histidine kinase homolog implicated in cytokinin signal transduction.
Science
274:
982-985
Kehoe DM, Grossman AR (1996) Similarity of chromatic adaptation sensor to phytochrome and ethylene receptors. Science 273: 1409-1412[Abstract]
Kieber JJ, Rothenberg M, Roman G, Feldmann KA, Ecker JR (1993) CTR1, a negative regulator of the ethylene response pathway in Arabidopsis, encodes a member of the raf family of protein kinases. Cell 72: 427-441[CrossRef][ISI][Medline]
Krems B, Charizanis C, Entian K-D (1996) The response regulator-like protein Pos9/Skn7 of Saccharomyces cerevisiae is involved in oxidative stress response. Curr Genet 29: 327-334[ISI][Medline]
Loomis WF, Shaulsky G, Wang N (1997) Histidine kinases in signal transduction pathways of eukaryotes. J Cell Sci 110: 1141-1145[Abstract]
Lowry DF,
Roth AF,
Rupert PB,
Dahlquist FW,
Moy FJ,
Domaille PJ,
Matsumura P
(1994)
Signal transduction in chemotaxis: a propagating conformational change upon phosphorylation of CheY.
J Biol Chem
269:
26358-26362
Lupas A,
Stock JB
(1989)
Phosphorylation of an N-terminal regulatory domain activates the CheB methylesterase in bacterial chemotaxis.
J Biol Chem
264:
17337-17342
Maeda T,
Takekawa M,
Saito H
(1995)
Activation of yeast PBS2 MAPKK by MAPKKKs or by binding of an SH3-containing osmosensor.
Science
269:
554-558
Maeda T, Wurgler-Murphy SM, Saito H (1994) A two-component system that regulates an osmosensing MAP kinase cascade in yeast. Nature 369: 242-245[CrossRef][Medline]
Makino K, Shinagawa H, Amamura M, Kawamoto T, Yamada M, Nakata A (1989) Signal transduction in the phosphate regulon of Escherichia coli involves phosphotransfer between PhoR and PhoB proteins. J Mol Biol 210: 551-559[CrossRef][Medline]
Min K-T,
Hilditch CM,
Diederich B,
Errington J,
Yudkin MD
(1993)
F, the first compartment-specific transcription factor of B. subtilis, is regulated by an anti- factor that is also a protein kinase.
Cell
74:
735-742[CrossRef][ISI][Medline]
Morgan BA, Banks GR, Toone WM, Raitt D, Kuge S, Johnson LH (1997) The Skn7 response regulator controls gene expression in the oxidative stress response of the budding yeast Saccharomyces cerevisiae. EMBO J 16: 1035-1044[CrossRef][ISI][Medline]
Morgan BA, Bouquin N, Merrill GF, Johnston LH (1995) A yeast transcription factor bypassing the requirement for SBF and DSC1/MBF in budding yeast has homology to bacterial signal transduction proteins. EMBO J 14: 5679-5689[ISI][Medline]
Ninfa AJ,
Magasanik B
(1986)
Covalent modification of the glnG product, NRI, by the glnL product, NRII, regulates the transcription of the glnALG operon in Escherichia coli.
Proc Natl Acad Sci USA
83:
5909-5913
Nixon BT,
Ronson CW,
Ausubel FM
(1986)
Two-component regulatory systems responsive to environmental stimuli share strongly conserved domains with nitrogen assimilation regulatory genes ntrB and ntrC.
Proc Natl Acad Sci USA
83:
7850-7854
Ota IM,
Varshavsky A
(1993)
A yeast protein similar to bacterial two-component regulators.
Science
262:
566-569
Page N, Sheraton J, Brown JL, Stewart RC, Bussey H (1996) Identification of ASK10 as a multicopy activator of Skn7p-dependent transcription of a HIS3 reporter gene. Yeast 12: 267-272[CrossRef][Medline]
Parkinson JS, Kofoid EC (1992) Communication modules in bacterial signaling proteins. Annu Rev Genet 26: 71-112[CrossRef][ISI][Medline]
Perego M, Hoch JA (1996) Protein aspartate phosphatases control the output of two-component signal transduction systems. Trends Genet 12: 97-101[CrossRef][Medline]
Popov KM,
Kedishvili NY,
Zhao Y,
Shimomura Y,
Crabb DW,
Harris RA
(1993)
Primary structure of pyruvate dehydrogenase kinase establishes a new family of eukaryotic protein kinases.
J Biol Chem
268:
26602-26606
Posas F, Wurgler-Murphy SM, Maeda T, Witten EA, Thai TC, Saito H (1996) Yeast HOG1 MAP kinase cascade is regulated by a multistep phosphorelay mechanisms in the SLN1-YPD1-SSK1 `two-component' osmosensor. Cell 86: 865-875[CrossRef][ISI][Medline]
Pratt LA, Silhavy TJ (1995) Porin regulation of Escherichia coli. In J Hoch, T Silhavy, eds, Two-Component Signal Transduction. ASM Press, Washington, DC, pp 105-128
Pratt LA,
Silhavy TJ
(1996)
The response regulator SprE controls the stability of RpoS.
Proc Natl Acad Sci USA
93:
2488-2492
Quail PH (1997) The phytochromes: a biochemical mechanism of signaling in sight? Bioessays 19: 571-579[CrossRef][ISI][Medline]
Sakakibara H, Suzuki M, Takei K, Deji A, Taniguchi M, Sugiyama T (1998) A response-regulator homolog possibly involved in nitrogen signal transduction mediated by cytokinin in maize. Plant J (in press)
Schaller GE,
Bleecker AB
(1995)
Ethylene-binding sites generated in yeast expressing the Arabidopsis ETR1 gene.
Science
270:
1809-1811
Schneider-Poetsch HAW, Braun B, Marx S, Schaumburg A (1991) Phytochromes and bacterial sensor proteins are related by structural and functional homologies. FEBS Lett 281: 245-249[CrossRef][ISI][Medline]
Schuster SC, Noegel AA, Oehme F, Gerisch G, Simon MI (1996) The hybrid kinase DokA is part of the osmotic response system of Dictyostelium. EMBO J 15: 3880-3889[ISI][Medline]
Shaulsky G,
Escalante R,
Loomis WF
(1996)
Developmental signal transduction pathways uncovered by genetic suppressors.
Proc Natl Acad Sci USA
93:
15260-15265
Shaulsky G, Fuller D, Loomis WF (1998) A cAMP-phospho-diesterase controls PKA-dependent differentiation. Development 125: 691-699[Abstract]
Shieh J-C,
Wilkinson MG,
Buck W,
Morgan BA,
Makio K,
Millar JBA
(1997)
The Mcs4 response regulator coordinately controls the stress-activated Wak1-Wis1-Sty1 MAP kinase pathway and fission yeast cell cycle.
Genes Dev
11:
1008-1022
Stock AM, Mottonen JM, Stock JB, Schutt CE (1989) Three-dimensional structure of CheY, the response regulator of bacterial chemotaxis. Nature 337: 745-749[CrossRef][Medline]
Stock JB, Lukat GS, Stock AM (1991) Bacterial chemotaxis and the molecular logic of intracellular signal transduction metworks. Annu Rev Biophys Biophys Chem 20: 109-136[CrossRef][ISI][Medline]
Stock JB, Stock AM, Mottonen JM (1990) Signal transduction in bacteria. Nature 344: 395-400[CrossRef][Medline]
Stock JB, Surette MG, Levit M, Park P (1995) Two-component signal transduction systems: structure-function relationships and mechanisms of catalysis. In J Hoch, T Silhavy, eds, Two-Component Signal Transduction. ASM Press, Washington, DC, pp 25-51
Tsuzuki M, Aiba H, Mizuno T (1994) Gene activation by the Escherichia coli positive regulator OmpR: phosphorylation-independent mechanism of activation by an OmpR mutant. J Mol Biol 242: 607-613[CrossRef][Medline]
Uhl MA, Miller JF (1996) Integration of multiple domains in a two-component sensor protein: the Bordetella pertussis BvgAS phosphorelay. EMBO J 15: 1028-1036[ISI][Medline]
Volz K (1993) Structural conservation in the CheY superfamily. Biochemistry 32: 11741-11753[CrossRef][Medline]
Volz K,
Matsumura P
(1991)
Crystal structure of Escherichia coli CheY refined at 1.7-A resolution.
J Biol Chem
266:
15511-15519
Wang N, Shaulsky G, Escalante R, Loomis WF (1996) A two component histidine kinase gene that functions in Dictyostelium development. EMBO J 15: 3890-3898[ISI][Medline]
Wanner BL (1994) Multiple controls of the Escherichia coli Pho regulon by the Pi sensor PhoR, the catabolite regulatory sensor CreC, and acetyl phosphate. In A Torriani-Gorini, E Yagil, S Silver, eds, Phosphate in Microorganisms: Cellular and Molecular Biology. ASM Press, Washington, DC, pp 12-21
Ward MJ, Zusman DR (1997) Regulation of directed motility in Myxococcus xanthus. Mol Microbiol 24: 885-893[CrossRef][ISI][Medline]
Wilkinson JQ,
Lanahan MB,
Yen H-C,
Giovannoni JJ,
Klee HJ
(1995)
Science
270:
1807-1809
Wurgler-Murphy SM, Saito H (1997) Two-component signal transducers and MAPK cascades. Trends Biochem Sci 22: 172-176[CrossRef][ISI][Medline]
Yeh K-C,
Wu S-H,
Murphy JT,
Lagarias JC
(1997)
A cyanobacterial phytochrome two-component light sensory system.
Science
277:
1505-1508
Yen H-C, Lee S, Tanksley SD, Lanahan MB, Klee HJ, Giovannoni JJ (1995) The tomato Never-ripe locus regulates ethylene-inducible gene expression and is linked to a homolog of the Arabidopsis ETR1 gene. Plant Physiol 107: 1343-1353[Abstract]
Zhou D, Kalaitzis P, Mattoo AK, Tucker ML (1996) The mRNA for an ETR1 homologue in tomato is constitutively expressed in vegetative and reproductive tissues. Plant Mol Biol 30: 1331-1338[CrossRef][ISI][Medline]
This article has been cited by other articles:
|
|
 |
|
  D. F. Aubert, R. S. Flannagan, and M. A. Valvano A Novel Sensor Kinase-Response Regulator Hybrid Controls Biofilm Formation and Type VI Secretion System Activity in Burkholderia cenocepacia Infect. Immun., May 1, 2008; 76(5): 1979 - 1991. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-T. Lin, T.-Y. Huang, W.-C. Liang, and H.-L. Peng Homologous Response Regulators KvgA, KvhA and KvhR Regulate the Synthesis of Capsular Polysaccharide in Klebsiella pneumoniae CG43 in a Coordinated Manner J. Biochem., September 1, 2006; 140(3): 429 - 438. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Zhang and L. Shi Distribution and evolution of multiple-step phosphorelay in prokaryotes: lateral domain recruitment involved in the formation of hybrid-type histidine kinases Microbiology, July 1, 2005; 151(7): 2159 - 2173. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. L. Catlett, O. C. Yoder, and B. G. Turgeon Whole-Genome Analysis of Two-Component Signal Transduction Genes in Fungal Pathogens Eukaryot. Cell, December 1, 2003; 2(6): 1151 - 1161. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
