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316

SA, JA, ethylene, and disease resistance in plants
Xinnian Dong
Exciting advances have been made during the past year:
isolating mutants affecting plant disease resistance, cloning
genes involved in the regulation of various defense responses,
and characterizing novel defense signaling pathways. Recent
studies have demonstrated that jasmonic acid and ethylene
are important for the induction of nonspecific disease
resistance through signaling pathways that are distinct from
the classic systemic acquired resistance response pathway
regulated by salicylic acid.

Addresses
Developmental, Cell, and Molecular Biology Group, Department of
Botany, LSRC Building, PO Box 91000, Duke University, Durham,
NC 27708-1000, USA; e-mail: xdong@acpub.duke.edu
Current Opinion in Plant Biology 1998, 1:316–323
http://biomednet.com/elecref/1369526600100316
 Current Biology Ltd ISSN 1369-5266

Abbreviations
Avr
avirulence
BTH
benzo(1,2,3)thiadiazole-7-carbothioic acid S-methyl ester
eds
enhanced disease susceptibility
HR
hypersensitive response
INA
2,6-dichloroisonicotinic acid
ISR
induced systemic resistance
JA
jasmonic acid
MAP
mitogen-activated protein
ndr
non-race-specific disease resistance
pad

phytoalexin deficient
PR
pathogenesis-related
R
resistance
SA
salicylic acid
SAR
systemic acquired resistance

Introduction
The battle between a plant and an invading pathogen
is often dependent on speed. The winner is determined
by how quickly the pathogen can proliferate and exert
damage, compared to how fast the plant can respond
with the necessary levels of defense. If a pathogen is
immediately recognized by a plant, for example when
a plant has a specific resistance (R) gene that interacts
with the corresponding avirulence (avr) gene from the
pathogen, a rapid defense mechanism known as the

hypersensitive response (HR) occurs to prevent infection
[1–6]. A lack of rapid pathogen recognition often leads
to a successful infection. In addition to this immediate,
one-on-one contest, plants also employ general resistance
mechanisms induced after an HR or during a successful
infection to combat secondary infections from a broad
spectrum of pathogens or to prevent an existing infection
from spreading further. One such general defense mechanism is known as systemic acquired resistance (SAR)
[7–9]. SAR induction requires the signal molecule salicylic
acid (SA), which accumulates in plants prior to the onset

of SAR. Removal of SA in transgenic plants expressing
salicylate hydroxylase (encoded by the bacterial nahG
gene) prevents the establishment of SAR [10]. In some
plants such as tobacco, cucumber, and Arabidopsis, SA is
not only necessary but also sufficient for the induction of
SAR. Treatment of these plants with SA or its functional
analogs such as 2,6-dichloroisonicotinic acid (INA) and
benzo(1,2,3)thiadiazole-7-carbothioic acid S-methyl ester
(BTH) induces SAR [11,12]. SAR is believed to be a result

of the concerted activation of pathogenesis-related (PR)
genes [13–16]; overexpression of a single PR gene only
provides limited protection to the plant [17–21]. Even
though their roles in disease resistance have yet to be
clearly demonstrated, expression levels of PR genes serve
as convenient markers for monitoring SAR.
Characterization of SAR in a variety of plant species has
suggested the existence of a complex signaling network
that involves many factors affecting various aspects of general disease resistance. It has become evident that plants
utilize multiple pathways to transduce pathogenic signals
to activate HR, SAR, and other resistance responses,
and that SA-mediated SAR is not the only pathway that
can lead to broad-spectrum disease resistance. Evidence
is emerging that strongly suggests the importance of
jasmonic acid (JA) and ethylene as alternative signals in
the induction of resistance against microbial pathogens, in
addition to their well-characterized roles in the wounding
response in plants. In this review, I focus on the genetic
and molecular experiments carried out in the past year that
define the signaling components in both SA-dependent

and SA-independent acquired resistance.

Different signaling pathways leading to the
induction of resistance
Genetic screens performed in Arabidopsis have generated
several classes of mutants which define potential signaling
components downstream of the avr-R recognition event.
One group of mutants, represented by eds1 (for enhanced
disease susceptibility) [22] and ndr1 (for non-race-specific
disease resistance) [23], exhibit altered responses to
multiple avr signals. The recessive eds1 mutation lacks
the capability for signal transduction from a subset
of R genes resulting in susceptibility to strains of
Peronospora parasitica and Pseudomonas syringae carrying the
corresponding avr genes. The ndr1 mutation appears to
influence the function of a different subset of R genes
causing a loss of resistance to Pseudomonas syringae pv.
tomato DC3000 carrying the bacterial avirulence genes
avrRpt2, avrB, or avrPph3. The requirement for EDS1
or NDR1 by different sets of R genes seems to be

mutually exclusive (JE Parker, personal communication).
It has been proposed, therefore, that separate signaling
components are used in different avr-R interactions. The

SA, JA, ethylene, and disease resistance in plants Dong

selective use of a signaling component may be based
on the structure of an individual R gene, with each
R gene within a class sharing a particular component.
Connections between these early signaling components
and the downstream SA or JA and ethylene signaling
pathways have yet to be established. The recent success
in cloning the EDS1 gene which encodes a lipase (JE
Parker, personal communication) and the NDR1 gene
which encodes a protein with two putative transmembrane
domains [24••] will certainly lead to new information on
the molecular functions of these genes.
A new class of mutants, designated dnd (for defense, no
death), do not show HR after inoculation with P. syringae
expressing avrRpt2 or avrRpm1 but maintain resistance to

this pathogen (AF Bent, personal communication). The
identification of dnd mutants may imply that cell death
is not essential for avr–R specific resistance. Another
plausible explanation is that the resistance observed in
dnd mutants is a result of the downstream activation of
the SAR response, signified by the constitutively elevated
levels of SA and PR gene expression in these mutant
plants.
Analysis of mutants that form HR-like lesions in the
absence of pathogen infection and display enhanced
nonspecific pathogen resistance has yielded additional
insights into regulation of resistance responses. The
Arabidopsis LSD1 gene encodes a novel zinc finger protein
which may respond to superoxide accumulated during the
HR to restrict the spreading of cell death [25••]. The
maize Lls1 gene has been found to encode a protein
with two conserved substrate binding motifs of aromatic
ring-hydroxylation dioxygenases and probably functions
to degrade a phenolic mediator of cell death [26••]. The
Mlo gene of barley is predicted to be a membrane bound

protein with at least six membrane-spanning helices [27••].
Further characterization of these genes, in addition to
the genes defined by the HR-compromised mutants, may
provide clues as to how signals are produced during an HR
leading to the induction of systemic resistance. Epistasis
analyses between the HR-compromised mutants and the
lesion mimic mutants may reveal the hierarchy of the
signaling events.
A recent report has shown convincingly that reactive oxygen intermediates generated during an HR may serve as
signals mediating the establishment of systemic resistance
[28••]. Alvarez et al. demonstrated that inoculation of
Arabidopsis with an avirulent pathogen triggers not only
an HR at the site of infection but also induces secondary
oxidative bursts in discrete clusters of cells in distant,
uninfected tissues, which ultimately lead to the formation
of microscopic HR lesions. Both the primary oxidative
burst and the reiterative secondary oxidative bursts in the
systemic tissues have been shown to be required for the
induction of SAR.

317

Virulent pathogens have also been used to identify
components of nonspecific resistance responses. Characterization of these mutants has shown that there is
a perception/signaling pathway for virulent pathogens
leading to SA accumulation and resistance that is distinct from that triggered by avirulent pathogens. The
eds mutants were isolated for their enhanced disease
susceptibility after infection by the virulent pathogen
P. syringae pv. maculicola ES4326 [29,30••]. Inoculation
of these mutant plants with an avirulent pathogen still
results in an HR and an SAR response even though
there is an upward shift in growth of the challenging
pathogen in both control plants, pre-treated with 10 mM
magnesium chloride, and induced plants, pre-inoculated
with an avirulent pathogen. In eds5-1, PR-1 gene induction
by the virulent pathogen Psm ES4326 is reduced to 10% of
the wild-type levels but is fully restored by SA treatment.
The pad mutants (for phytoalexin-deficient) are deficient
in accumulating camalexin, an indolic phytoalexin, after
infection by the virulent pathogen Psm ES4326 [31]

and pad4, specifically, appears to affect a regulatory
component in camalexin biosynthesis. The pad4 mutant
displays enhanced susceptibility to Psm ES4326 and a
number of isolates of P. parasitica [32•]. In addition, it
exhibits pleiotropic defects in Psm ES4326-induced SA
accumulation and PR gene expression that can be partially
reversed by the addition of SA [33••]. The pleiotropic
effects of pad4 are specific to the virulent pathogen Psm
ES4326 (and also Pst DC3000) because the synthesis of
camalexin, the accumulation of SA, and the expression of
PR-1 gene induced by Psm ES4326 carrying avrRpt2 are
all similar to wild-type in pad4.
Characteristics of all these mutants suggest the existence
of separate components involved in transducing diverse
signals generated by different pathogens. PAD4 and
EDS5 may be regulators controlled by signals produced
during a virulent infection while NDR1, EDS1, DND
and LSD1 may represent components involved in the
avr-induced HR, with NDR1 and EDS1 responding to
distinct avr-R interactions. Without further knowledge of

the signal molecules, however, classification of these signal
transducing components can only be done arbitarily. A
component identified in an avirulent pathogen-induced
response, such as eds1, may also affect the response to
a virulent pathogen. Nevertheless, all these components
seem to be involved in early signaling events. Whether
they play a direct role in the induction of SAR or other
general resistance responses has yet to be determined.

SA-dependent signaling pathway
In tobacco, Arabidopsis, and cucumber, an increase in
SA concentration leads to the onset of SAR [34–36],
but in other plants such as potato and rice, high levels
of SA are detected even under noninducing conditions
[37,38•,39]. It has been questioned whether SA is a signal
required for SAR in potato and rice, and if it is, how is

318

Plant–microbe interactions

the resistance response is activated in these plants with
constitutively high levels of SA. Using transgenic potato
plants expressing bacterial salicylate hydroxylase (which
metabolises SA), it has recently been demonstrated that
SA is required for arachidonic acid-induced resistance to
Phytophthora infestans in potato. The resistance, however, is
induced as a result of an increase in sensitivity to SA rather
than an increase in SA synthesis [40••]. The mechanism of
this induction is unknown; it could occur by increasing the
accessibility of SA to a receptor, or by inducing synthesis
or activity of an SA receptor.
Biochemical approaches used to identify components
involved in the transduction of the SA signal have
produced promising candidates. An SA binding protein
has been identified [41•] which has a 150-fold higher
affinity for SA than catalase: catalase being the first SA
binding protein isolated using 14C-labeled SA. Protein
phosphorylation and dephosphorylation have been indicated in various defense responses including SA-regulated
PR gene expression [42]. Consistent with these results, a
mitogen-activated protein (MAP) kinase has been shown
to be activated in an SA-induced tobacco suspension
cell extract [43••]. The sequence of this p48SIP kinase
(SA-induced protein kinase) is distinct from other plant
MAP kinases previously implicated in stress responses.
In addition to the biochemical approaches, genetic screens
performed in Arabidopsis have uncovered one locus, NPR1
(for nonexpresser of PR genes; also called NIM1 or
SAI1), that clearly functions downstream of SA [29,44–46].
NPR1 has been cloned independently by two research
groups [47••,48••]. Sequence analysis of the gene and
its twelve mutant alleles has shown that NPR1 contains
a functionally important ankyrin-repeat domain which
may be involved in protein–protein interaction. The
carboxyl end of NPR1, where a nuclear localization signal
(NLS) resides, has also been shown to be essential
for protein function. The importance of this NLS has
been demonstrated by the strict nuclear localization of a
biologically active NPR1-GFP fusion protein after SAR
induction (M Kinkema, X Dong, unpublished data). SAR
induction not only modestly increases NPR1 levels, but
also is required for activation of the NPR1 protein.
Overexpression of NPR1 in Arabidopsis confers significant
resistance to strains of P. syringae and P. parasitica that
are normally virulent on wild-type Arabidopsis [49••]. By
measuring the induction kinetics of the PR genes during
the infection, it has been demonstrated that PR genes are
not constitutively expressed in the NPR1-overexpressing
lines and that pathogen infections cause a stronger,
but not faster, expression of these genes compared to
wild-type. These characteristics make NPR1 a favorable
target for genetic engineering of disease resistance in
crops, because constitutive activation of SAR would be
likely to have detrimental effects on plant growth and
also might result in high selection pressure for more
virulent pathogens. There are still many questions that

remain to be answered with regard to the molecular
function of NPR1. For example, it is unknown if NPR1
regulates PR gene expression through activation of a
positive transcription factor, or inactivation of a negative
transcription factor. To completely understand NPR1
function, the NPR1-interacting component(s) will have to
be identified and characterized.

JA- and ethylene-dependent signaling
pathway
An exciting new development in the past year is the
discovery of SA-independent pathway(s) that also lead to
broad-spectrum, systemic resistance. Both JA and ethylene
have been shown to be important for the induction of
these alternative responses. Fortunately, there already
exists a wealth of information about the role of JA
in plants response to wounding and insect attack [50].
The wound-induced octadecanoid pathway results in the
synthesis of the signal molecule JA and subsequent
activation of proteinase inhibitor genes. In addition to JA,
ethylene has recently been shown to be a required, though
not sufficient, signal that acts with JA to induce the wound
response in tomato [51]. Ethylene is produced rapidly
and transiently in leaves after injury or upon induction
by JA or cell wall oligosaccharide fragments. Inhibition
of ethylene production or sensitivity through mutation,
antisense technology, or the use of chemical inhibitors all
negatively affect induction of the JA pathway.
The JA regulated wound- and insect-induced pathway has
long been thought to be involved in conferring resistance
to microbial pathogens because it is also induced by
oligosaccharide fragments released by the action of lytic
enzymes produced by an invading pathogen; however,
the role of ethylene and JA in plant disease resistance
seemed at times to be ambiguous. For example, in
the Arabidopsis ethylene-insensitive mutant ein2, disease
symptoms caused by Pst DC3000, Psm 4326, and Xanthomonas campestris pv. campestris were shown to be reduced
while growth of these pathogens remained unaffected
[52,53]. In the same ethylene-insensitive mutant, the
involvement of ethylene in SA-mediated SAR was ruled
out because SA- and INA-induced PR-1 gene expression
and resistance to P. parasitica were shown to be unaffected
by the mutation [54]. In fact, the basal levels of PR-1
mRNA seemed to be higher in the ein2 mutant than in
the wild-type. Similar results have recently been obtained
using the tomato Never ripe mutant impaired in ethylene
perception [55•]. In another example, the Arabidopsis coi1
mutants identified for their insensitivity to coronatine and
methyl JA (a volatile form of JA) were shown to be
resistant to a bacterial pathogen producing the phytotoxin
coronatine [56]; however, this result is inconsistent with
the hypothesis that methyl JA induces disease resistance.
These results can be explained if the ethylene/JA pathway
negatively affects the SA pathway. When the ethylene/JA
pathway is blocked in the ein2 and coil mutants, the SA
pathway may be slightly upregulated, leading to elevated

SA, JA, ethylene, and disease resistance in plants Dong

levels of PR gene expression and increased tolerance to
bacterial pathogens.
A more clear-cut connection between systemic disease resistance, JA and ethylene signaling molecules has recently
been established in Arabidopsis by the characterization of
the systemically inducible antimicrobial peptides, thionin
Thi2.1 and defensin PDF1.2 [57,58]. The expression
of Thi2.1 is induced by methyl JA, silver nitrate, and
Fusarium oxysporum f. sp. matthiolae, but not by SA
[57]. The antimicrobial activity of thionin has been
demonstrated in Arabidopsis by the enhanced resistance
to F. oxysporum sp matthiolae observed in transgenic plants
overexpressing the Thi2.1 gene [59•]. The PDF1.2 gene is
induced by JA, ethylene, rose bengal, and the non-host
pathogen Alternaria brassicicola [58]. The induction of
PDF1.2 by A. brassicicola is inhibited in the JA-insensitive
mutant coi1 and in the ethylene-insensitive mutant ein2,
indicating that JA and ethylene are required for the
induction. PDF1.2 expression, however, is unaffected in
nahG transgenic plants which are unable to accumulate
SA, in the npr1 mutant which is insensitive to SA
induction, or in the cpr1 mutant which has elevated levels
of SA and constitutive SAR. It is evident that PDF1.2
and Thi2.1 represent end products of a systemically
expressed resistance pathway(s) that is distinct from the
SA-dependent SAR and is potentially regulated by both
JA and ethylene.
Genetic studies have shown that JA and ethylene are
essential signals in another resistance response known
as induced systemic resistance (ISR) that is established
after treatment with various strains of root-colonizing
biocontrol bacteria Pseudomonas fluorescens (CMJ Pieterse,
personal communication). ISR is effective against the
virulent Pst DC3000 and F. oxysporum f. sp. raphani and
functions independently of SA and PR gene expression
[60,61•]. Intriguingly, during ISR, PDF1.2 is not induced,
suggesting that JA and ethylene may regulate ISR through
a pathway different from that which includes PDF1.2 and
Thi2.1. ISR, therefore, appears to be a novel systemic
resistance response in plants that can be triggered in roots
by rhizobacteria and is regulated by JA and ethylene.

Interactions between different resistant
pathways
The antagonistic relationship between the JA and SA
pathways has been well documented in the studies of
wound responses in plants [50,62]. The inhibitory effect of
SA on the proteinase inhibitor genes is partially overcome
by pretreatment of plants with both JA and ethylene, but
not by either signal alone [51]. This further supports the
notion that both ethylene and JA are required signals for
wound responses and implies that SA inhibits not only
the synthesis of JA and ethylene but also a signaling step
downstream of JA and ethylene.
Interactions between the different pathways are also evident in plant resistance responses to microbial organisms.

319

For example, in tobacco, treatments with SA and the
pathogenic Erwinia carotovora or Erwinia-derived elicitors
seem to induce two distinct pathways leading to the
expression of separate sets of genes [63•]. Erwinia-derived
elicitors antagonize the SA-mediated induction of PR
genes while SA inhibits the induction of Erwinia-activated
genes. Such antagonism suggests the presence of common
regulatory components for both pathways, and possibly
signifies the evolution of a mechanism designated to
prioritize different resistance responses.
Common regulatory components have been found in separate signaling pathways. In the root-colonizing bacteriuminduced ISR, which is SA-independent but JA- and
ethylene-dependent, the function of NPR1 has been
shown to be essential (CMJ Pieterse, personal communication). This implies that NPR1 not only plays a
key regulatory role in SAR but also participates in the
JA- and ethylene-regulated, SA-independent ISR. This is
consistent with the detection of high levels of NPR1 in
roots (H Cao, M Kinkema, X Dong, unpublished data)
where ISR is induced and where PR gene expression and
SAR are absent [64].
Other components potentially shared by the SA-induced
SAR and the JA- and ethylene-induced disease resistance
pathways have been identified through epistasis analyses
between Arabidopsis mutants with enhanced resistance and
mutants with compromised defense responses. The cpr5
mutant expresses both the PR genes and the PDF1.2,
and Thi2.1 genes, and is resistant to Psm ES4326 and
P. parasitica Noco2. In the cpr5:npr1 double mutant, the
expression of PR genes and resistance to Psm ES4326 are
abolished while the expression of PDF1.2 and resistance
to P. parasitica remain unaffected [65••]. These results
suggest that a mutation in a single gene can upregulate
an NPR1-dependent pathway and an NPR1-independent
pathway, both of which can provide resistance to P.
parasitica. This conclusion is supported by the epistasis
analysis performed in the cpr1:npr1 double mutant. In cpr1,
where only the NPR1-dependent pathway is activated, the
enhanced resistance to P. parasitica is completely abolished
by npr1 in the cpr1:npr1 double mutant (SA Bowling, X
Dong, unpublished data).
Analyses of the dominant, gain-of-resistance Arabidopsis
mutant cpr6 define another possible point of interaction
between the SA-regulated and the JA- and ethylene-regulated pathways [66••]. Similar to cpr5, the cpr6 mutant
displays enhanced levels of PR and PDF1.2 gene expression. In the cpr6:npr1 double mutant, however, neither
PR nor PDF1.2 gene expression is significantly affected
by npr1. Even though it is difficult to determine the
precise position of cpr6 in the disease resistance signaling
network, the data suggest a dual role for cpr6 in regulating
both the PR and PDF1.2 genes. Perhaps the wild-type
CPR6 works with NPR1 to induce the expression of
PR genes, and the dominant cpr6 mutation renders

320

Plant–microbe interactions

The relationship between the SA-regulated SAR and the
JA- and ethylene-regulated disease resistance needs to
be explored further using mutants of both pathways.
For example, epistasis analysis between the cpr5 or cpr6
mutant and the ethylene-insensitive mutant, ein2, or the
jasmonic acid-non-responsive mutant, jar1 [67], will be
carried out and the results will be compared with those of
cpr5:npr1 or cpr6:npr1. Preliminary analysis of the cpr5:ein2
and cpr6:ein2 double mutants have indicated that a full

the protein NPR1-independent. The interplay between
CPR6, NPR1 and the two distinct signaling pathways has
been further suggested by the complete suppression of
PDF1.2 expression by INA treatment observed in cpr6,
in comparison to only a partial suppression of PDF1.2
expression in the cpr6:npr1 double mutant. A functional
NPR1 protein seems to be required for INA to sequester
all the mutant cpr6 protein thereby preventing activation
of PDF1.2.

Figure 1

Wounding,
Wall fragments

Avirulent pathogen

Virulent pathogen

CPR5
NDR1
EDS1
DNDs
LSD1

PAD4
EDSs

?

ROS
HR

?

Ethylene

CPR1

JA

SA
?

EIN2

COI1, JAR1

CPR6

NPR1
(In roots)

Wound response

PDF1.2, Thi2.1
Resistance to
P. parasitica

ISR

PR genes
SAR:
resistance to
P. parasitica
Psm ES4326
LAR
Current Opinion in Plant Biology

A working model of pathways leading to broad-spectrum disease resistance in plants. The Arabidopsis genes defined by the mutants described
in this review are presented. After plant–pathogen recognition, multiple signaling components (CPR5, NDR1, EDS1, DNDs, LSD1) are employed
that lead to the formation of reactive oxygen species (ROS) and HR, and the synthesis of SA. NDR1 and EDS1 are involved in transducing
signals from separate subsets of avr-R interactions, the relative positions of other genes have yet to be determined. It is also unknown whether
these genes (except CPR5) are involved in the JA- and ethylene-mediated resistant responses. (This ambiguity is represented by a dashed line.)
Virulent pathogens can also induce SA synthesis and local resistance, probably through separate regulatory components such as PAD4 and
EDSs. Further downstream, the CPR1-SA-NPR1 linear pathway has been demonstrated by various genetic analyses. The pathway of JA and
ethylene is proposed on the basis of the wound response in tomato [51], showing that JA and ethylene induce each other’s synthesis and that
JA and ethylene are both required for activating the wound response, PDF1.2 and Thi2.1 gene expression, resistance to P. parasitica, and ISR. It
remains to be determined whether these responses (shown in rectangular boxes) share regulatory components downstream of JA and ethylene.
The SA pathway and the JA/ethylene pathway may interact antagonistically, with SA inhibiting both the synthesis and the signal transduction of
JA and ethylene (illustrated with blocked lines). The possible involvement of NPR1 in the SA-independent but JA- and ethylene-dependent ISR
is intriguing. Further characterization of NPR1 and another Arabidopsis component CPR6, which is involved in regulating the expression of both
PR and PDF1.2 genes, should provide new insight into the relationship of these pathways.

SA, JA, ethylene, and disease resistance in plants Dong

induction of PDF1.2 in cpr5 and cpr6 requires the function
of EIN2 and probably ethylene (JD Clarke, X Dong,
unpublished data).

References and recommended reading
Papers of particular interest, published within the annual period of review
have highlighted as:

• of special interest
•• of outstanding interest

Conclusions
Isolation of different classes of mutants affecting nonspecific disease resistance and characterization of various plant
defense responses have revealed a complex and interesting
network of pathways that function both separately and
together to render broad-spectrum protection to plants.
At the center of this network are the signal molecules
SA, JA, and ethylene. A model, with the Arabidopsis
genes described in this review highlighted, is represented
here to stimulate more discussion (Figure 1). After
plant–pathogen recognition, multiple signaling components (CPR5, NDR1, EDS1, DNDs, LSD1) are employed
that lead to the formation of reactive oxygen species (ROS)
and HR, and the synthesis of SA. While NDR1 and EDS1
are involved in transducing signals from separate subsets
of avr-R interactions, the relative positions of other genes
have yet to be determined. It is also unknown whether
these genes (except CPR5) are involved in the JA- and
ethylene-mediated resistant responses. Virulent pathogens
can also induce SA synthesis and local resistance, probably
through separate regulatory components such as PAD4
and EDSs. Further downstream, the CPR1-SA-NPR1
linear pathway has been demonstrated by various genetic
analyses. The pathway of JA and ethylene is proposed on
the basis of the wound response in tomato [51] showing
that JA and ethylene induce each other’s synthesis and that
JA and ethylene are both required for activating the wound
response, PDF1.2 and Thi2.1 gene expression, resistance
to P. parasitica, and ISR. It remains to be determined
whether these responses share regulatory components
downstream of JA and ethylene. The SA pathway and the
JA/ethylene pathway may interact antagonistically, with SA
inhibiting both the synthesis and the signal transduction
of JA and ethylene. The possible involvement of NPR1
in the SA-independent but JA- and ethylene-dependent
ISR is intriguing. Further characterization of NPR1 and
another Arabidopsis component CPR6, which is involved
in regulating the expression of both PR and PDF1.2 genes,
should provide new insight into the relationship of these
pathways.
A complete understanding of these signaling events
calls for co-operation between laboratories working on
different resistance responses. As more epistasis tests are
carried out between different classes of mutants, new
resistance-related phenotypes will be revealed and used
to perform more in-depth analyses. Information from
both genetic and molecular research will be combined
to establish a more comprehensive outline of the disease
resistance network in plants.

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Acknowledgments
I would like to thank AF Bent, J Glazebrook, JE Parker, CMJ Pieterse, AD
Shapiro for communicating unpublished work and JD Clarke, J Glazebrook,
M Kinkema, JN Siedow for helpful suggestions on this review.

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