REVIEWS
TIBS 24 – NOVEMBER 1999
Phosphorelay signal
transduction: the emerging
family of plant response
regulators
Ingrid B. D’Agostino and Joseph J. Kieber
Homologs of bacterial two-component signal transduction elements are
emerging as key players in eukaryotic signaling systems. The recent
identification of a large gene family in Arabidopsis that is similar to twocomponent response regulators emphasizes the importance of this signaling mechanism in plants. The understanding of the function of these
response regulator genes is only rudimentary but the transcriptional induction of a subset by cytokinin suggests a role for some of these regulators
in the response to this important plant hormone.
BACTERIA SENSE AND respond to
environmental cues using a conserved
signaling cascade known as the twocomponent system, which generally
consists of a sensor kinase that perceives environmental stimuli and a response regulator that propagates the
signal, often by directly regulating
the transcription of target genes1–4. The
sensor histidine kinase is usually a
membrane-bound protein that contains
two distinct domains, the input and
transmitter domains (see Fig. 1a).
Detection of a signal via the input domain results in either the inhibition or
the activation of the histidine kinase
activity of the transmitter domain. Active
sensor kinases are dimers that transphosphorylate on a conserved histidine
residue in the transmitter domain. This
phosphate is then transferred to a conserved aspartate residue in the receiver
domain of a cognate response regulator.
Most response regulators also contain
output domains that act as transcription factors. Over 40 different twocomponent systems have been identified
in Escherichia coli alone5, each responding to distinct environmental stimuli.
A variation of the relatively simple,
two-component system is the multistep
I. B. D’Agostino is in the Dept of Biological
Sciences, Laboratory for Molecular Biology,
University of Illinois at Chicago, Chicago,
IL 60607, USA; and J. J. Kieber is in the Dept
of Biology, University of North Carolina,
Chapel Hill, NC 27599-3280, USA.
Email: [email protected].
452
phosphorelay6,7 (Fig. 1b). The common
link between multi-step phosphorelays is
that they involve four sequential phosphorylation events that alternate between histidine and aspartate residue
substrates, although the number of proteins that harbor these phosphorylation
sites varies. For example, in the pathway
that regulates sporulation in Bacillus
subtilis, the trans-phosphorylation of a
set of sensor kinases on histidine is followed by the transfer of the phosphate to
the Spo0F receiver domain on an aspartate residue8. The phosphate is then
transferred to a histidine residue on
Spo0B, a protein that shares no sequence
similarity with sensor kinases. Finally,
the phosphate is transferred to an aspartate residue on Spo0A, which is a typical
response regulator. Thus, the phosphorylated amino acid residues reside on
four separate proteins. In the phosphorelay system that regulates low-oxygen
responsiveness in E. coli, the ArcB sensor
kinase contains, in addition to the transmitter domain, a fused receiver and a histidine phosphotransfer domain (HPt)9.
HPt domains are phosphorylated on a
histidine residue by upstream receiver
domains and, in contrast to receiver and
transmitter domains, they do not exhibit
any catalytic activity but rather act as an
intermediate in the His–Asp phosphorelay6,7. Thus, in the Arc system, the first
three phosphotransfers occur on a single
protein. The final phosphorylation event
is on a separate response regulator
protein, called ArcA.
The first eukaryotic two-component
system elements identified were the
Arabidopsis ETR1 gene10, involved in
ethylene signaling (Box 1), and the
Saccharomyces cerevisiae SLN1 gene,
which plays a role in osmosensing11,12.
The yeast osmosensing system is a
phosphorelay comprised of three proteins: the SLN1 sensor kinase, fused to a
receiver domain, a HPt protein (YPD1)
and a response regulator protein (SSK1).
The fusion of a receiver domain to the
SLN1 transmitter domain is a typical
arrangement for most eukaryotic sensor
kinases, a structure that has been
termed a hybrid kinase13. ETR1 is the
founding member of an ethylene receptor family comprised of five genes in
Arabidopsis14–16. Like ETR1, the EIN4 and
ETR2 genes encode predicted hybrid
kinases but the ERS1 and ERS2 paralogs
lack a receiver domain. There are at
least five additional sensor kinases in
Arabidopsis, one of which, CKI1, has
been implicated in cytokinin signaling17,18 (Box 1).
Recently, independent receiver domains similar to bacterial responseregulator proteins have been identified
in several plants, including Arabidopsis19–21, maize22, Brassica napus23 and
rice19. These genes were identified in
screens for transcripts responsive to
the hormone cytokinin and to nitrogen
starvation, by searching expressed sequence tag (EST) and genomic sequence
databases, and in a screen for
transcripts that are upregulated during
B. napus pod development. The
Arabidopsis response-regulator (ARR)
gene family is the most thoroughly characterized and will be the focus of this
review.
Phylogenetic analysis of plant response
regulators
There are at least 14 distinct Arabidopsis genes that encode proteins, that
are similar in sequence to response regulators and that contain the two invariant aspartate and the invariant lysine
residues at the appropriate positions
(Table 1). These have been given a variety of names, but for clarity and consistency the nomenclature assigned by
Imamura et al.24 (ARR1–ARR14; see
Table 1) will be used in this review.
Comparison of the predicted amino acid
sequences of the receiver domains
using phylogenetic analysis reveals that
these ARR genes fall into at least two
distinct clades, termed type A and type
B (Fig. 2). Consistent with this phylogenetic comparison, the two types are
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distinguishable by additional criteria:
type-A proteins lack the large C-terminal
extension that is fused to the receiver
domains of the type-B proteins (Fig. 2),
and the type-A genes are induced by
exogenous cytokinin application and
nitrate treatment, whereas the type-B
genes are not (see below). The ARR13
gene does not fit closely into either of
these clades by sequence comparison
but it has a predicted domain structure
similar to the type-B genes. The receiver
domains that are fused to the
Arabidopsis ETR1 and CKI1 sensor kinases are only distantly related to the
receiver domains present in the ARRs.
This phylogenetic analysis revealed
that the maize and rice response-regulator homologs that have been identified clearly fall into the type-A clade.
Consistent with this designation, expression of the maize homolog is induced by both cytokinin and nitrate22. In
addition, a clone was identified in the
cotton EST database that belongs to the
type-A clade (GhARR1). From this analysis, one would predict that the cotton
and rice genes are also regulated by
cytokinin. Interestingly, although the
B. napus response regulator homolog
(SAC29) has a structure similar to that
of the type-A genes, it is more similar in
sequence to the receiver domains of
CKI1 and ETR1 (Fig. 2).
Type-A response regulators
The predicted amino acid sequences
and domain structures of the seven
Arabidopsis type-A ARR genes are most
similar to CheY, a bacterial response
regulator protein that lacks an output
domain1. However, type-A ARRs have an
insertion of 12 amino acids in the
receiver domain not present in CheY,
as well as unique C-terminal extensions19,21. The predicted amino acid sequences of the receiver domains of the
type-A proteins are extremely similar to
each other in their primary sequence,
with amino acid identities ranging from
60% to 93%. The type-A proteins differ
from each other primarily in their Cterminal domains, which are all less
than 100 amino acids long. ARR5 and
ARR6 have small C-terminal extensions
(,30 amino acids). ARR7 has a highly
charged and serine-rich carboxy extension. The extensions of ARR3, ARR4,
ARR8 and ARR9 are highly acidic and
the ARR3 and ARR4 extensions are also
serine- and proline-rich.
The ARR4 and ARR5 genes were isolated in a screen for transcripts that
were rapidly induced by the plant
(a)
Input
P
P
H
D
Transmitter
Receiver
Sensor kinase
Output
Response regulator
(b)
P
P
P
P
H
D
H
D
Hybrid kinase
AHPs
ARRs
Ti BS
Figure 1
(a) Basic prokaryotic two-component system. The input domain (red) is responsible for perceiving external stimuli that can serve either to activate or inactivate the histidine kinase
activity of the attached transmitter domain (green). Active sensor kinases act as dimers
that trans-phosphorylate themselves on a histidine residue (H). For the sake of simplicity,
only a monomer of the sensor kinase is depicted. The phosphate is then transferred to a
conserved aspartate residue (D) in the receiver domain (blue) of a cognate response regulator, which results in either the activation or the inactivation of an output domain (yellow).
(b) Model for a potential phosphorelay system in plants. The input domain of a hybrid
kinase, such as ETR1 or CKI1, regulates the activity of the transmitter domain, which, when
active, autophosphorylates on a histidine residue. The phosphate is then transferred to an
aspartate residue on the fused receiver domain and then to a histidine on an AHP protein
(purple) and, finally, to an aspartate residue on an ARR protein. The first and the final phosphorylation events have been demonstrated to occur in vitro30,31 but the other two have not
yet been detected. Abbreviations: AHP, Arabidopsis gene that encodes a histidine
phosphotransfer (HPt) domain; ARR, Arabidopsis response regulator.
hormone cytokinin19. Further analysis
revealed that induction was indeed
extremely fast (,10 minutes), insensitive to inhibition of protein synthesis
and specific for cytokinin19. These characteristics indicate that ARR4 and ARR5
might be cytokinin primary response
genes, possibly involved in cytokinin
signaling. Consistent with this notion,
work by Kakimoto has implicated a sensor kinase, CKI1, in cytokinin signaling18
(see Box 1), which raises the possibility
that these ARR genes could act downstream of CKI1. Recently, the other typeA ARR genes (ARR3, ARR6, ARR7, ARR8
and ARR9) were also found to be induced by cytokinin25,26. Like ARR4 and
ARR5, induction of ARR6 and ARR7 is
rapid, whereas ARR3, ARR8 and ARR9
appear to respond more slowly to exogenous cytokinin. Several of the type-A
ARR transcripts are also elevated upon
nitrate application to nitrogen-starved
plants25, which could reflect an alteration in cytokinin content in response to
changing nitrogen levels.
Expression of ARR4 and ARR5 was
also found to be sensitive to environmental stresses such as salt treatment,
dehydration and a decrease in temperature20. However, the kinetics of this induction have not yet been determined.
In untreated Arabidopsis plants, transcripts for the type-A ARR genes are
generally detected in all adult organs,
with the highest expression in roots
usually, although there are minor differences in the spatial expression patterns
of the various family members.
Genes similar to type-A response
regulators have also been identified in
other higher plants (Fig. 2). The sequence of a cytokinin-inducible gene,
ZmCip1 (renamed ZmRR1), is most similar to the Arabidopsis type-A response
regulators22. Treatment of maize leaves
with cytokinin resulted in an increase in
the steady-state level of both ZmRR1
mRNA and protein. Supply of nitrate to
the roots of nitrogen-starved plants
also resulted in accumulation of ZmRR1
transcript and protein, similar to
453
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Box 1. The role of sensor kinases in plant signal tansduction
Ethylene is a gaseous plant hormone involved in diverse plant growth and developmental processes, such as fruit ripening, root hair initiation,
leaf and floral senescence, and abscission. The signaling pathway for ethylene has been elegantly dissected in Arabidopsis using a genetic
screen based on a response of etiolated seedlings to ethylene known as the triple response (reviewed in Ref. 16). The ethylene receptor is
encoded by a family of genes that are similar to bacterial two-component sensor kinases. These genes were first identified by a series of
dominant mutations that resulted in ethylene insensitivity39. The receptors fall into two classes: those similar to hybrid kinases in that they
contain a receiver domain fused to the input and transmitter domains (ETR1, ETR2 and EIN4), and those that lack a fused receiver domain
(ERS1 and ERS2). Binding of ethylene occurs within a three-pass transmembrane domain at the N-terminal end of the receptors40 and is likely
to involve a copper moiety that is added by a protein similar to the Wilson–Menkes copper ATPase41,42. Histidine kinase activity of ETR1 has
been demonstrated in vitro, which suggests that these receptors could function in a manner similar to those in bacterial systems31.
Interestingly, genetic analysis indicates that, in the absence of the hormone, these receptors inhibit ethylene signaling and that binding of
ethylene turns on the response pathway by inactivating the receptors37. A likely downstream target of the ethylene receptors is CTR1, a Raf
kinase homolog that is also a negative regulator of ethylene signaling36. In animal cells, the major function of Raf is to regulate the activity of a
second protein kinase, MAP kinase kinase, which in turn regulates the activity of MAP kinase. Many homologs of both MAP kinase kinase and
MAP kinase have been found in plants but it is not clear which, if any, are involved in ethylene signaling34. In contrast to Raf, which is activated
by a small G-protein known as Ras, CTR1 might be regulated directly by the ethylene receptors, as ETR1 has been demonstrated to bind to CTR1
using yeast two-hybrid studies and in vitro co-immunoprecipitation experiments43. However, it is possible that other components, such as
response-regulator homologs, are involved in this regulation of CTR1 activity by ETR1 isoforms. Additional elements that act downstream of
CTR1 have also been identified, including a transcription factor gene family44,45.
A sensor kinase could also play a role in the signaling pathway for the cytokinin plant hormones. Cytokinins are N6-substituted adenine
derivatives that have been implicated as regulators of many plant processes including cell division, apical dominance, leaf senescence, and
sink/source relationships46. Kakimoto identified CKI1 as a gene that, when overexpressed, can confer on tissue culture cells the ability to
proliferate in the absence of added cytokinin18. Sequence analysis revealed that the predicted CKI1 protein had a structure similar hybrid
sensor kinases. CKI1 has a unique N-terminal extension that contains two predicted transmembrane-spanning domains. If CKI1 is actually a
cytokinin receptor, then the inferred extracellular loop spanned by the two transmembrane domains is likely to be the site of cytokinin binding.
observations with Arabidopsis type-A
ARR genes. A gene identified in B. napus,
using differential display, which is induced during pod dehiscence, has a
domain structure similar to type-A
ARRs, in that it lacks an extensive Cterminal extension downstream of the
receiver domain23. However, as noted
above, this SAC29 gene displays only
very weak similarity to the receiver domains of other type-A ARRs, and there is
no evidence that it is regulated by
cytokinin or nitrate.
Type-B response regulators
There are at least seven type-B response regulators in Arabidopsis (Table
1) that are characterized by the similar-
ity of their receiver domains (an exception being ARR13; see Fig. 2) and the
presence of a large C-terminal extension,
which ranges in size from 260 to 500
amino acids. In contrast to the other
type-B genes, the ARR12, ARR13 and
ARR14 genes were identified solely from
genomic sequences and no corresponding cDNAs have as yet been identified24.
The predicted amino acid sequences of
the receiver domains of the various
type-B ARRs are 60–96% identical (excluding ARR13). In contrast, the type-B
receivers are only 24–30% identical to
the predicted amino acid sequences of
the type-A ARRs. The long C-terminal extension of the type-B ARRs varies widely
in sequence among the seven proteins
Table 1. Arabidopsis response regulators
Inducing conditionsa
Gene
Type A
ARR3
ARR4
ARR5
ARR6
ARR7
ARR8
ARR9
Type B
ARR1
ARR2
ARR10
ARR11
ARR12–ARR14
Alternative name
IBC7/ATRR1
IBC6/ATRR2
ATRR3
ATRR4
ARP5
ARP4
ARP3
Cytokinin
Nitrate
Chromosome
Ref.
1
11
111
11
111
1
1
1
1
11
11
1
1
1
I
I
III
V
?
II
?
21
19–21
19–21
20,21
20,21
20
20
2
2
2
nt
nt
2
2
2
nt
nt
?
IV
IV
?
II
28
28
24,27
24,27
24
1, weak induction; 11, moderate induction; 111, the highest relative induction; 2, indicates no
induction; nt, not tested.
a
454
but has some common features, which
suggests that these proteins might act
as transcription factors (see below).
Neither cytokinin nor nitrogen affect
the expression of the type-B ARR genes
that have been examined (ARR1, ARR2,
ARR10 and ARR11) and it has been postulated that this might be a property
common to all type-B ARR genes24,26,27.
Furthermore, the expression of these
ARR genes is not affected by exogenous
application of a number of other plant
hormones, including abscisic acid
(ABA), auxin, gibberillin (GA), ethylene
and methyl-jasmonate26,27. The type-B
ARR genes that have been examined
display distinct spatial patterns of
expression, although, generally, they are
present in all adult organs at detectable
levels20,27. One notable exception is root
tissue, in which ARR10 and ARR11 transcripts are not detected27, but which
contains the highest levels of ARR1 and
ARR2 transcripts28.
ARR signaling
Several studies have addressed
whether the ARR proteins exhibit
phosphorylation characteristics similar
to those of other response regulators
involved in His–Asp phosphorelays.
Imamura et al. examined whether ARR3,
ARR4 and ARR6 could effectively
compete with an endogenous E. coli
response regulator, OmpR, as a substrate for phosphorylation by a mutated
ArcB hybrid sensor kinase in vivo21. This
was tested by determining the expression of ompC, a target gene for OmpR,
REVIEWS
TIBS 24 – NOVEMBER 1999
using an ompC::lacZ fusion in strains
carrying plasmids that express various
combinations of ARRs and OmpR. The
expression of the ARR genes was found
to cause a decrease in activation of
OmpR by ArcB, as determined by
decreased β-galactosidase activity, presumably as a result of the ARRs competing with OmpR for phosphorylation by
ArcB. These results suggest that ARR3,
ARR4 and ARR6 are capable of acting
as phospho-acceptors from a sensor
kinase in E. coli. However, this conclusion
should be viewed with caution, as it was
not determined directly whether the
ARR proteins were actually phosphorylated in this somewhat artificial system.
Further evidence that the ARR proteins function in a phosphorelay comes
from in vitro studies employing Arabidopsis genes that encode predicted HPt
domains. Three such genes, called AHP1
(or ATHP3), AHP2 (or ATHP1) and AHP3
(or ATHP2)29,30, were identified by in
silico analysis by searching with the
YPD1 sequence. A fourth gene with high
similarity to the three published sequences is present in the sequence
of chromosome 3 from Arabidopsis
(I. B. D’Agostino and J. J. Kieber, unpublished; Accession number AAB63642.1).
These genes have been shown to rescue
the growth defect of a yeast strain
harboring an insertion in the YPD1
gene and are therefore presumed to be
authentic HPt domains. Purified AHP1
or AHP2 proteins, which had been
phosphorylated using crude bacterial
membranes, could transfer phosphate
to several purified type-A ARR proteins
in vitro24,30. Additionally, the AHPs have
been shown to interact with several
of the ARRs in the yeast two-hybrid system (Ref. 24 and I. B. D’Agostino and
J. J. Kieber, unpublished), further supporting the notion that these elements
form a functional interaction. A model
consistent with these results suggests
that the AHP proteins act as intermediates between hybrid sensor kinases,
such as ETR1 or CKI1, and the ARR
genes (see Fig. 1). However, it is important to note that whereas ETR1 has been
demonstrated to possess intrinsic histidine kinase activity31 using an autophosphorylation assay, the phosphorylation of an Arabidopsis HPt domain
by a hybrid kinase has not yet been
demonstrated.
Most bacterial two-component response regulators function by directly
regulating transcription1,4. Although it is
unlikely that the type-A ARRs contain
output domains, several lines of evidence
(a)
Type A
ARR10
ARR12
ARR11
GhRR1
ARR9 OsRR1
ARR8
ZmRR1
ARR4
ARR3
ARR5
ARR7 ARR6
ARR1
ARR2
ARR14
Type B
ARR13
SAC29
CKI1
ETR1
(b)
Type A
Receiver domain
Type B
B motif
Hybrid
kinases
Input domain
Transmitter domain
Ti BS
Figure 2
(a) The plant response regulator gene family. An unrooted phylogenetic tree was derived using
the predicted amino acid sequence of the receiver domains from a variety of plant genes. The
tree was generated using the AllAll program at Molecular Biology Computational Resource at
the Baylor College of Medicine (http://cbrg.inf.ethz.ch/subsection3_1_1_.html). This
program generates trees using a least-squared, heuristic method38. The lengths of the
branches correspond to the Point Accepted Mutation (PAM) distances between the sequences. The ARR genes correspond to the Arabidopsis response regulators (see Table 1).
The cotton (GhRR1) sequence was obtained by searching the EST database for sequences
similar to ARR5 (I. B. D’Agostino and J. J. Kieber, unpublished). The rice sequence (OsRR1) is
from a previously sequenced EST clone19. SAC29 (Ref. 23) and ZmRR1 (Ref. 22) (a new designation for ZmCip1) are from Brassica napus and maize, respectively. The receiver domains
from the CKI1 and ETR1 hybrid sensor kinase are included for comparison. The accession
numbers for the sequences used in this analysis, as well as the corresponding residues (in
parentheses) are as follows: GhRR1 (4–125), AI055247; OsRR1 (1–69), D24560; note that
the rice and cotton sequences are from ESTs and are not full length; SAC29 (16–131),
AF057027; ZmRR1 (37–154), AB004882; CKI1 (986–1115), D87545; ETR1 (610–724),
P49333; ARR1 (37–150), AB016471; ARR2 (28–141), AB016472/ATAJ5196; ARR3
(33–158), AB008486; ARR4 (34–159), AB008487/AB010915/AF057282; ARR5 (25–151),
AB008488/AB010916/AF057281; ARR6 (25–150), AB008489; ARR7 (24–149), AB008490;
ARR8 (9–142), AB010917; ARR9 (9–144), AB010918; ARR10 (17–130), ATAJ51905/
AJ005195; ARR11 (11–124), ATAJ5194/AJ005194; ARR12 (17–130), ATF13D4; ARR13
(16–131), AC005623; ARR14 (11–125) AC006069. (b) Domain structure of plant proteins
that contain receiver-like domains (blue). The B motif (purple) is similar to sequences present
in the Myb family of transcription factors.
suggest that the C-terminal domains of
the type-B ARRs function as transcription factors. All seven contain an 80amino-acid stretch that is similar to a
Myb-related motif found in some novel
plant proteins24,28. This conserved domain is referred to as the ‘B motif’ and is
thought to bind to DNA (Ref. 28). Using a
PROPSEARCH comparison, Lohrmann et
al. noted that, based on amino acid composition, ARR10 and ARR11 are likely to
be related to the chick CTF4 and the
Xenopus L-MYC2 bHLH transcription
factors27. Finally, the amino acid sequences from several of the type-B,
C-terminal extensions are rich in proline
and glutamine residues, a feature often
observed in eukaryotic activation
domains. Consistent with these observations, the C-terminal domain of ARR11,
but not ARR4 (a type-A ARR), can activate transcription when fused to the
GAL4-DNA binding domain27. Further evidence indicating that these type-B ARR
proteins might act as transcription factors is the presence of a potential nuclear
localization signal in the C-terminal
domain, a feature not found in type-A
ARRs (Refs 27,28 and I. B. D’Agostino
and J. J. Kieber, unpublished). Transient
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REVIEWS
transformation of GFP fusions into parsley protoplasts has recently shown that
both ARR10 and ARR11 are indeed nuclear-localized proteins27. Thus, it is
very likely that the type-B ARRs act as
transcription factors and that the C-terminal portions of these proteins act as
output domains.
A potential downstream effector of
the type-A ARRs, which do not appear to
be transcription factors, based on their
primary amino acid sequence, was identified in a two-hybrid screen with ARR4
(Ref. 32). This analysis identified clones
identical to the previously identified
AtDBP gene, which encodes an auxinregulated, lysine-rich, non-specific DNAbinding protein33. The interaction was
confirmed by in vitro binding assays.
Although the function of AtDBP is unknown, these results make it a candidate
for a downstream target or an upstream
regulator of ARR4.
Other possible downstream effectors
of the type-A ARRs are elements of the
mitogen-activated protein (MAP) kinase
cascade34,35. In yeast, the SSK2 protein
kinase, which controls the activity of
a downstream MAP kinase cascade, is
regulated by the activity of the SLN1–
YPD–SSK1 phosphorelay12. In ethylene
signaling, CTR1, a Raf homolog [a MAP
kinase kinase kinase (MAPKKK)], has
been shown to act downstream of the
ETR1 family of sensor kinases36. There
are multiple MAPKKK genes in
Arabidopsis, a subset of which might be
regulated by the ARRs.
TIBS 24 – NOVEMBER 1999
tification of response-regulator proteins
and HPt proteins supported this idea.
Whereas some of the phosphotransfer
reactions predicted from prototypical
phosphorelays have tentatively been
demonstrated with plant enzymes, confirmation that these proteins work in a
manner analogous to their prokaryotic
counterparts awaits further biochemical studies of purified constituents.
With at least ten sensor kinases, 14
response regulators and four phosphotransfer proteins identified thus far, and
more likely to be uncovered as the sequencing of the Arabidopsis genome
continues, there is a vast number of
combinations of potential interactions.
It is possible that many of these elements participate in distinct signaling
pathways, although results from the
ETR1 sensor-kinase family suggest that
at least some of these have redundant
or overlapping functions37 and that the
ARRs participate only in a limited number of signaling cascades. There is much
to be learned about this burgeoning
gene family in plants, and with the
array of tools becoming available to
Arabidopsis researchers, these ARR
genes might soon reveal their secrets.
Acknowledgements
The authors would like to thank
T. Mizuno and K. Harter for preprints
and the National Science Foundation
(grant no. MCB-9816914 to J. J. K.) for
funding.
References
Conclusions and perspectives
What are the functions of the ARR
genes in vivo? Two likely possibilities
are ethylene and cytokinin signaling,
both of which have been shown to involve two-component sensor kinases.
The discovery that type-A ARR gene
expression is regulated by cytokinin
further strengthens this contention. The
similarity of certain domains of phytochromes (the red-light photoreceptors)
to the transmitter domain of sensor
kinases also raises the possibility that
the ARR genes could play a role in light
signaling. Confirmation of the function
of these genes is likely to come from
their disruption by insertion mutagenesis or from alterations of their in vivo
expression levels using transgenic
technology, or both.
The discovery of hybrid sensor kinases in Arabidopsis was the first indication that a His–Asp phosphorelay,
similar to those found in bacteria, could
operate in plants. The subsequent iden-
456
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