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At least 235 records · Page 13Linked to original sources
PubMed1998

The Notch signalling pathway in hair growth.

The Notch signalling pathway is an important mediator of cell fate selection whose involvement in epidermal appendage formation is now becoming recognised. Hair follicle development and hair formation involve the co-ordinated differentiation of several different cell types in which Notch appears to have a role. We report intricate expression patterns for the Notch-1 receptor and three ligands, Delta-1, Jagged-1 and Jagged-2 in the hair follicle. Notch-1 is expressed in ectodermal-derived cells of the follicle, in the inner cells of the embryonic placode and the follicle bulb, and in the suprabasal cells of the mature outer root sheath. Delta-1 is only expressed during embryonic follicle development and is exclusive to the mesenchymal cells of the pre-papilla located beneath the follicle placode. Expression of Jagged-1 or Jagged-2 overlaps Notch-1 expression at all stages. In mature follicles, Jagged-1 and Jagged-2 are expressed in complementary patterns in the follicle bulb and outer root sheath, Jagged-1 in suprabasal cells and Jagged-2 predominantly in basal cells. In the follicle bulb, Jagged-2 is localised to the inner (basal) bulb cells next to the dermal papilla which do not express Notch-1, whereas Jagged-1 expression in the upper follicle bulb overlaps Notch-1 expression and correlates with bulb cell differentiation into hair shaft cortical and cuticle keratinocytes.

Animals↗
PubMed1991

Intracellular signaling pathway of endothelin-1.

The intracellular signaling pathway of endothelin-1 (ET-1) was studied in individual mesangial cells (MCs) and vascular smooth muscle cells (VSMCs) using microspectrofluorimetry of fura-2 ([Ca2+]i), SPQ ([Cl-]i), and bisoxonol (membrane potential). ET-1 elicited a five-fold increase in [Ca2+]i that showed immediate and sustained phases. Both the Ca(2+)-free medium and nifedipine pretreatment curtailed the sustained phase of the response to ET-1. ET-1 resulted in sustained membrane depolarization of MCs and VSMCs. This depolarization was not attributed to Na influx, as Na-free medium did not abolish it. A Cl(-)-channel inhibitor, IAA-94, blunted the depolarization and sustained elevation of [Ca2+]i in response to ET-1. In aortic rings, both nifedipine and IAA-94 attenuated ET-1-induced contraction. No additivity in the effect of nifedipine and IAA-94 was detected. Studies of SPQ fluorescence changes induced by ET-1 revealed an immediate and sustained increase in fluorescence intensity consistent with the decrease in [Cl-]i. The sustained but not immediate increase in SPQ fluorescence was virtually abolished in Ca(2+)-free medium with or without pretreatment with the intracellular Ca2+ chelator BAPTA. In conclusion, we hypothesize that ET-1 results in Ca2+ mobilization and Ca(2+)-dependent and -independent activation of Cl- channels. Ensuing Cl- efflux causes membrane depolarization and, in turn, activation of voltage-gated Ca2+ channels in MCs and VSMCs. The latter results in sustained elevation of [Ca2+]i that is indispensable for the full-scale contractile response to ET-1.

Animals↗
PubMed1999

Jeg-3 human choriocarcinoma-induced immunosuppression: downregulation of interleukin-2, interleukin-2 receptor alpha-chain, and its Jak/Stat signaling pathway.

PROBLEM: The mechanisms of the immunosuppressive and immunosuppression-inducing capacities of Jeg-3 human choriocarcinoma cell line supernatants (HCSs) are not yet completely understood. The influence on interleukin (IL)-2, IL-4 and interferon (IFN)-gamma production; IL-2 receptor (IL-2R) alpha-, beta-, and gamma-chain; and the signaling pathway molecules Janus kinase (Jak)1, Jak3, signal transducers and activators of transcription (Stat)1, Stat3, and Stat5 should be investigated. METHOD OF STUDY: For assessment of IL production, whole peripheral venous blood from healthy donors was stimulated with phorbol-myristate-acetate and ionomycine. Secretion of ILs was blocked with monensine. Intracellular ILs were analyzed by flow cytometry. For IL-2R and signaling pathway molecule analysis, peripheral blood lymphocytes were stimulated with phytohemagglutinin (PHA). IL-2R chains were measured by flow cytometry, and Jaks/Stats by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot. RESULTS: Phorbol-myristate-acetate and ionomycine strongly increase the percent-age of IL-2+ cells; an additional 50% HCSs significantly suppresses the percentage to, or below the level of unstimulated cells. IFN-gamma production is strongly decreased by HCSs in some cases, but not in others. PHA stimulates IL-2R alpha-, beta-, and gamma-chain expression and their signaling pathway molecules Jak1, Jak3, Stat1, Stat3, and Stat5. 50% HCS downregulates the alpha-chain and slightly upregulates the beta-chain. Jak1, Jak3, Stat1, Stat3, and Stat5 expression is suppressed approximately to, or below the level of unstimulated cells. CONCLUSIONS: HCS forcefully blocks the production of IL-2; the IL-2R alpha-chain; and Jak1, Jak3, Stat1, Stat3, and Stat5 expression. The observed phenomena might be caused by downregulation of an IL-2R regulation gene, and might play a key role in the expansion of choriocarcinoma, and possibly in the survival of the fetal allograft.

Adult↗
PubMed1996

Destabilization of Raf-1 by geldanamycin leads to disruption of the Raf-1-MEK-mitogen-activated protein kinase signalling pathway.

The serine/threonine kinase Raf-1 functions downstream of Rats in a signal transduction cascade which transmits mitogenic stimuli from the plasma membrane to the nucleus. Raf-1 integrates signals coming from extracellular factors and, in turn, activates its substrate, MEK kinase. MEK activates mitogen-activated protein kinase (MAPK), which phosphorylates other kinases as well as transcription factors. Raf-1 exists in a complex with HSP90 and other proteins. The benzoquinone ansamycin geldanamycin (GA) binds to HSP90 and disrupts the Raf-1-HSP90 multimolecular complex, leading to destabilization of Raf-1. In this study, we examined whether Raf-1 destabilization is sufficient to block the Raf-1-MEK-MAPK signalling pathway and whether GA specifically inactivates the Raf-1 component of this pathway. Using the model system of NIH 3T3 cells stimulated with phorbol 12-myristate 13-acetate (PMA), we show that GA does not affect the ability of protein kinase C alpha to be activated by phorbol esters, but it does block activation of MEK and MAPK. Further, GA does not decrease the activity of constitutively active MEK in transiently transfected cells. Finally, disruption of the Raf-1-MEK-MAPK signalling pathway by GA prevents both the PMA-induced proliferative response and PMA-induced activation of a MAPK-sensitive nuclear transcription factor. Thus, we demonstrate that interaction between HSP90 and Raf-1 is a sine qua non for Raf stability and function as a signal transducer and that the effects observed cannot be attributed to a general impairment of protein kinase function.

3T3 Cells↗
PubMed1996

Activation of the cAMP-dependent signaling pathway downregulates the expression of interleukin-3 and granulocyte-macrophage colony-stimulating factor in activated human T lymphocytes.

Expression of cytokines by T lymphocytes is a highly balanced process, involving stimulatory and inhibitory intracellular signaling pathways. We have examined the modulating effects of the cAMP-dependent signaling pathway on the expression of interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in activated human T lymphocytes. 2'-O-dibutyryl-cAMP (db-cAMP), prostaglandin E2 (PGE2), isoproterenol (ISO), and isobutyl-methyl-xantin (IBMX) costimulated with concanavalin A (Con A) or Con A plus the phorbolester phorbol myristate acetate (PMA) inhibited IL-3 and GM-CSF mRNA accumulation compared to the effects of Con A or Con A plus PMA alone. Nuclear run-on experiments revealed that the inhibitory effect of db-cAMP could partially be ascribed to a five-fold reduction in transcription rate of both the IL-3 and GM-CSF gene in the presence of Con A or Con A plus PMA. mRNA stability studies demonstrated that PMA increased the stability of both transcripts. db-cAMP did not affect the stability of IL-3 and GM-CSF mRNAs in Con A activated cells. In contrast, in Con A plus PMA activated cells, db-cAMP significantly reduced the half-life of both transcripts: IL-3 >240 minutes vs. 90 minutes and GM-CSF 90 minutes vs. 60 minutes. Finally, in accordance with the mRNA data, db-cAMP, PGE2, and ISO reduced the secretion of IL-3 and GM-CSF protein in Con A and Con A plus PMA activated cells. In conclusion, these data demonstrate that the protein kinase A (PKA)-dependent signaling pathway is an important regulatory mechanism in controlling IL-3 and GM-CSF gene expression in activated human T lymphocytes.

1-Methyl-3-isobutylxanthine↗
PubMedDate not supplied

PEST sequences in proteins involved in cyclic nucleotide signalling pathways.

There is growing evidence that PEST sequences act as proteolytic recognition signals within polypeptides. PEST sequences are rich in proline (P), glutamic acid (E), serine (S), and threonine (T) and can be identified by the PEST-FIND program. Both the catalytic and regulatory subunits of the cAMP-dependent protein kinase have been shown to have conditional PEST sequences which are exposed upon cAMP binding to the enzyme. cAMP binding leads to rapid dissociation of C- and R-subunits, and both subunits have increased sensitivity to proteolysis. It is not known whether other proteins that participate in the cyclic nucleotide signalling pathway have PEST regions in their amino acid sequences. Therefore, we have screened amino acid sequences of proteins that are directly involved in cyclic nucleotide cascade, including cGMP-dependent protein kinases, anchoring proteins for cAMP-dependent protein kinase, cyclic nucleotide-gated ion channels, and cyclic nucleotide phosphodiesterases, for PEST sequences using the PEST-FIND program. Many PEST sequences with high scores have been identified in these proteins. The occurrence of the PEST sequences is very high in proteins involved in cyclic nucleotide signalling pathways (approximately 80%). This value is much higher than the percentage (10%) of PEST sequences that can be found in the primary structures of the proteins listed in the data bank. This frequent occurrence of PEST sequences in proteins involved in cyclic nucleotide action and metabolism suggests an important role of proteolysis of these key proteins of signal transduction.

Adenylyl Cyclases↗
PubMed1994

Related target enhancers for dorsal and NF-kappa B signaling pathways.

Drosophila dorsoventral (DV) patterning and mammalian hematopoiesis are regulated by related signaling pathways (Toll, interleukin-1) and transcription factors (dorsal, nuclear factor-kappa B). These factors interact with related enhancers, such as the rhomboid NEE and kappa light chain enhancer, that contain similar arrangements of activator and repressor binding sites. It is shown that the kappa enhancer can generate lateral stripes of gene expression in transgenic Drosophila embryos in a pattern similar to that directed by the rhomboid NEE. Drosophila DV determinants direct these stripes through the corresponding mammalian cis regulatory elements in the kappa enhancer, including the kappa B site and kappa E boxes. These results suggest that enhancers can couple conserved signaling pathways to divergent gene functions.

Animals↗
PubMed1998

MyD88 is an adaptor protein in the hToll/IL-1 receptor family signaling pathways.

The Toll-mediated signaling cascade using the NF-kappaB pathway has been shown to be essential for immune responses in adult Drosophila, and we recently reported that a human homolog of the Drosophila Toll protein induces various immune response genes via this pathway. We now demonstrate that signaling by the human Toll receptor employs an adaptor protein, MyD88, and induces activation of NF-kappaB via the Pelle-like kinase IRAK and the TRAF6 protein, similar to IL-1R-mediated NF-kappaB activation. However, we find that Toll and IL-1R signaling pathways are not identical with respect to AP-1 activation. Finally, our findings implicate MyD88 as a general adaptor/regulator molecule for the Toll/IL-1R family of receptors for innate immunity.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Wingless inactivates glycogen synthase kinase-3 via an intracellular signalling pathway which involves a protein kinase C.

The Drosophila gene product Wingless (Wg) is a secreted glycoprotein and a member of the Wnt gene family. Genetic analysis of Drosophila epidermal development has defined a putative paracrine Wg signalling pathway involving the zeste-white 3/shaggy (zw3/sgg) gene product. Although putative components of Wg- (and by inference Wnt-) mediated signalling pathways have been identified by genetic analysis, the biochemical significance of most factors remains unproven. Here we show that in mouse 10T1/2 fibroblasts the activity of glycogen synthase kinase-3 (GSK-3), the murine homologue of Zw3/Sgg, is inactivated by Wg. This occurs through a signalling pathway that is distinct from insulin-mediated regulation of GSK-3 in that Wg signalling to GSK-3 is insensitive to wortmannin. Additionally, Wg-induced inactivation of GSK-3 is sensitive to both the protein kinase C (PKC) inhibitor Ro31-8220 and prolonged pre-treatment of 10T1/2 fibroblasts with phorbol ester. These findings provide the first biochemical evidence in support of the genetically defined pathway from Wg to Zw3/Sgg, and suggest a previously uncharacterized role for a PKC upstream of GSK-3/Zw3 during Wnt/Wg signal transduction.

Androstadienes↗
PubMed2000

A fundamental role for the nitric oxide-G-kinase signaling pathway in mediating intercellular Ca(2+) waves in glia.

In this study, we highlight a role for the nitric oxide-cGMP-dependent protein kinase (NO-G-kinase) signaling pathway in glial intercellular Ca(2+) wave initiation and propagation. Addition of the NO donor molsidomine (100-500 microM) or puffing aqueous NO onto primary glial cell cultures evoked an increase in [Ca(2+)](i) in individual cells and also local intercellular Ca(2+) waves, which persisted after removal of extracellular Ca(2+). High concentrations of ryanodine (100-200 microM) and antagonists of the NO-G-kinase signaling pathway essentially abrogated the NO-induced increase in [Ca(2+)](i), indicating that NO mobilizes Ca(2+) from a ryanodine receptor-linked store, via the NO-G-kinase signaling pathway. Addition of 10 microM nicardipine to cells resulted in a slowing of the molsidomine-induced rise in [Ca(2+)](i), and inhibition of Mn(2+) quench of cytosolic fura-2 fluorescence mediated by a bolus application of 2 microM aqueous NO to cells, indicating that NO also induces Ca(2+) influx in glia. Mechanical stress of individual glial cells resulted in an increase in intracellular NO in target and neighboring cells and intercellular Ca(2+) waves, which were NO, cGMP, and G-kinase dependent, because incubating cells with nitric oxide synthase, guanylate cyclase, and G-kinase inhibitors, or NO scavengers, reduced Delta[Ca(2+)](i) and the rate of Ca(2+) wave propagation in these cultures. Results from this study suggest that NO-G-kinase signaling is coupled to Ca(2+) mobilization and influx in glial cells and that this pathway plays a fundamental role in the generation and propagation of intercellular Ca(2+) waves in glia.

Aminoquinolines↗
PubMed2000

Neuronal calcium activates a Rap1 and B-Raf signaling pathway via the cyclic adenosine monophosphate-dependent protein kinase.

Activity-dependent regulation of neuronal events such as cell survival and synaptic plasticity is controlled by increases in neuronal calcium levels. These actions often involve stimulation of intracellular kinase signaling pathways. For example, the mitogen-activated protein kinase, or extracellular signal-regulated kinase (ERK), signaling cascade has increasingly been shown to be important for the induction of gene expression and long term potentiation. However, the mechanisms leading to ERK activation by neuronal calcium are still unclear. In the present study, we describe a protein kinase A (PKA)-dependent signaling pathway that may link neuronal calcium influx to ERKs via the small G-protein, Rap1, and the neuronal Raf isoform, B-Raf. Thus, in PC12 cells, depolarization-mediated calcium influx led to the activation of B-Raf, but not Raf-1, via PKA. Furthermore, depolarization also induced the PKA-dependent stimulation of Rap1 and led to the formation of a Rap1/B-Raf signaling complex. In contrast, depolarization did not lead to the association of Ras with B-Raf. The major action of PKA-dependent Rap1/B-Raf signaling in neuronal cells is the activation of ERKs. Thus, we further show that, in both PC12 cells and hippocampal neurons, depolarization-induced calcium influx stimulates ERK activity in a PKA-dependent manner. Given the fact that both Rap1 and B-Raf are highly expressed in the central nervous system, we suggest that this signaling pathway may regulate a number of activity-dependent neuronal functions.

Animals↗
PubMed1994

Two cAMP receptors activate common signaling pathways in Dictyostelium.

Multiple signal transduction pathways within a single cell may share common components. In particular, seven different transmembrane helix receptors may activate identical pathways by interacting with the same G-proteins. Dictyostelium cells respond to cAMP using one such receptor, cAR1, coupled by a typical heterotrimeric G-protein to intracellular effectors. However, cells in which the gene for cAR1 has been deleted are unexpectedly still able to respond to cAMP. This implies either that certain responses are mediated by a different receptor than cAR1, or alternatively that a second, partially redundant receptor shares some of the functions of cAR1. We have examined the dose response and ligand specificity of one response, cAMP relay, and the dose response of another, cyclic GMP synthesis. In each case, the EC50 was approximately 100-fold higher and the maximal response was smaller in car1- than wild-type cells. These data indicate that cAR1 normally mediates responses to cAMP. The ligand specificity suggests that the responses seen in car1- mutants are mediated by a second receptor, cAR3. To test this hypothesis, we constructed a cell line containing deletions of both cAR1 and cAR3 genes. As predicted, these lines are totally insensitive to cAMP. We conclude that the functions of the cAR1 and cAR3 receptors are partially redundant and that both interact with the same heterotrimeric G-protein to mediate these and other responses.

Adenylyl Cyclases↗
PubMed1999

Negative regulation of N-cadherin-mediated cell-cell adhesion by the estrogen receptor signaling pathway in rat pituitary GH3 cells.

The ability of the estrogen receptor signaling pathway to regulate cell-cell adhesion, and N-cadherin and beta-catenin expression was examined in rat somatolactotropic GH3 cells cultured in serum-free, phenol red-free medium (SFM). Estradiol-17beta (E2) promoted a nonadherent phenotype, whereas the steroidal antiestrogen, ICI 182,780, induced the formation of tightly adherent aggregates of cells. The antiestrogen-induced cell-cell adhesion was associated with the presence of adherens junctions, and was Ca2+-dependent. E2 reduced surface N-cadherin protein to barely detectable levels, whereas ICI 182,780-treated cells displayed abundant punctate immunoreactive N-cadherin. Antiestrogen failed to induce adhesion in the presence of a blocking antibody to N-cadherin. ICI 182,780 increased the protein levels for N-cadherin and the cadherin-binding protein, beta-catenin, by twofold over SFM controls or E2-treated samples. ICI 182,780 also increased the mRNA levels for N-cadherin and beta-catenin by two- to fivefold. In GH3 cells cultured in growth medium, ICI 182,780 increased N-cadherin and beta-catenin levels by twofold over untreated controls, and inhibited cell proliferation by 53%. These results provide the first demonstration of the regulation of N-cadherin-mediated cell-cell adhesion by the estrogen receptor (ER) signaling pathway in pituitary somatolactotrophs through the coordinate regulation of N-cadherin and beta-catenin expression. The inverse relationship between ICI 182,780-induced adhesion and proliferation raises the possibility that these two processes are functionally related.

Animals↗
PubMed1996

Stimulation of the P-450 side chain cleavage enzyme (CYP11A1) promoter through ras- and Ets-2-signaling pathways.

Expression of the ovine P-450 side-chain cleavage enzyme gene (CYP11A1) is stimulated by epidermal growth factor (EGF) through a pathway that involves c-Jun in JEG-3 placental cells. Growth factor signaling involves ras-dependent and ras-independent signaling pathways, which in turn regulate gene transcription through related but distinct mitogen-activated protein kinase pathways (MAPKs) including the extracellular signal-regulated kinases (ERKs) and the stress-activated protein kinases (SAPKs). We investigated the intracellular signaling pathways governing EGF induction of the CYP11A1 promoter. EGF stimulation of the CYP11A1 promoter (4-fold) was reduced 60% by a dominant negative mutant of ras (N17), and 30-40% by antisense ras. EGF induced both ERK and SAPK activity in JEG-3 cells. EGF-induced CYP11A1 promoter activity was reduced 60% by the MEK1 inhibitor PD098059 and 50% by a dominant negative mutant of the ERK-specific regulator MEK1. In contrast, dominant negative mutants of the SAPK-specific activator, SEK1, induced a further increase in EGF-induced CYP11A1 promoter activity. Constitutively active mutants of ras (V12 or L61) increased CYP11A1 promoter activity 6- to 8-fold. Deletion of the EGF response element (EGF-RE) between -92 and -77 bp reduced ras induction by 60%; however, a residual 3-fold induction remained through the proximal -77 bp. Mutation of the EGF-RE AP-1-like sequence in the context of the native promoter reduced CYP11A1 promoter activation by ras 60%. The EGF-RE sequence was sufficient for 6-fold activation by ras in the context of an heterologous thymidine kinase promoter. Candidate transcription factor targets (c-Jun, c-Ets-2) for the ras-signaling cascade were examined for their effects on CYP11A1 promoter activity. Overexpression of c-Jun induced the CYP11A1 promoter through the EGF-RE; however, c-Ets-2 activation of the CYP11A1 promoter (12-fold) required the proximal ras-responsive promoter sequences that are distinct from the EGF/MEK/c-Jun-responsive element. Induction of the CYP11A1 promoter by EGF involves a ras/MEK1/AP-1-dependent pathway that is distinct from induction by ras/c-Ets-2.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1997

Regulation of gliogenesis in the central nervous system by the JAK-STAT signaling pathway.

A mechanism by which members of the ciliary neurotrophic factor (CNTF)-leukemia inhibitory factor cytokine family regulate gliogenesis in the developing mammalian central nervous system was characterized. Activation of the CNTF receptor promoted differentiation of cerebral cortical precursor cells into astrocytes and inhibited differentiation of cortical precursors along a neuronal lineage. Although CNTF stimulated both the Janus kinase-signal transducer and activator of transcription (JAK-STAT) and Ras-mitogen-activated protein kinase signaling pathways in cortical precursor cells, the JAK-STAT signaling pathway selectively enhanced differentiation of these precursors along a glial lineage. These findings suggest that cytokine activation of the JAK-STAT signaling pathway may be a mechanism by which cell fate is controlled during mammalian development.

Animals↗
PubMed1998

The cellular response to oxidative stress: influences of mitogen-activated protein kinase signalling pathways on cell survival.

The mammalian response to stress is complex, often involving multiple signalling pathways that act in concert to influence cell fate. To examine potential interactions between the signalling cascades, we have focused on the effects of a model oxidant stress in a single cell type through an examination of the relative influences of mitogen-activated protein kinases (MAPKs) as well as two proposed apoptosis regulators, nuclear factor kappaB (NF-kappaB) and Bcl-2, in determining cell survival. Treatment of HeLa cells with H2O2 resulted in a time- and dose-dependent induction of apoptosis accompanied by sustained activation of all three MAPK subfamilies: extracellular signal-regulated protein kinase (ERK), c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) and p38. This H2O2-induced apoptosis was markedly enhanced when ERK2 activation was selectively inhibited by PD098059. Apoptosis decreased when JNK/SAPK activation was inhibited by expression of a dominant negative mutant form of SAPK/ERK kinase 1. Inhibition of the p38 kinase activity with p38-specific inhibitors SB202190 and SB203580 had no effect on cell survival. Because NF-kappaB activation by H2O2 is potentially related to both the ERK and JNK/SAPK signalling pathways, we examined the effects of inhibiting the activation of NF-kappaB; this interference had no effect on the cellular response to H2O2. Overexpression of the anti-apoptotic protein Bcl-2 significantly decreased the apoptosis seen after treatment with H2O2 without altering ERK or JNK/SAPK activities. Our results suggest that ERK and JNK/SAPK act in opposition to influence cell survival in response to oxidative stress, whereas neither p38 nor NF-kappaB affects the outcome. Bcl-2 acts independently and downstream of ERK and JNK/SAPK to enhance the survival of H2O2-treated cells.

3T3 Cells↗
PubMed1998

The unfolded protein response: an intracellular signalling pathway with many surprising features.

The unfolded protein response (UPR) is an intracellular signalling pathway--originating in the endoplasmic reticulum (ER) and leading to the cell nucleus--that controls transcription of genes encoding ER-resident proteins. Recent developments in this field show that this pathway utilizes unique regulatory mechanisms, including translational attenuation and a regulated mRNA splicing step catalysed by a bifunctional transmembrane kinase/endoribonuclease and tRNA ligase. This review describes the characterization of the UPR signalling pathway, focusing on the novel regulatory mechanisms that it has revealed.

Endoplasmic Reticulum↗
PubMed2001

A fatty acid desaturase modulates the activation of defense signaling pathways in plants.

Salicylic acid (SA) plays an important role in activating various plant defense responses, including expression of the pathogenesis-related (PR) genes and systemic acquired resistance. A critical positive regulator of the SA signaling pathway in Arabidopsis is encoded by the NPR1 gene. However, there is growing evidence that NPR1-independent pathways can also activate PR expression and disease resistance. To elucidate the components associated with NPR1-independent defense signaling, we isolated a suppressor of the npr1-5 allele, designated ssi2. The recessive ssi2 mutation confers constitutive PR gene expression, spontaneous lesion formation, and enhanced resistance to Peronospora parasitica. In contrast, a subset of defense responses regulated by the jasmonic acid (JA) signaling pathway, including expression of the defensin gene PDF1.2 and resistance to Botrytis cinerea, is impaired in ssi2 plants. With the use of a map-based approach, the SSI2 gene was cloned and shown to encode a stearoyl-ACP desaturase (S-ACP DES). S-ACP DES is an archetypical member of a family of soluble fatty acid (FA) desaturases; these enzymes play an important role in regulating the overall level of desaturated FAs in the cell. The activity of mutant S-ACP DES enzyme was reduced 10-fold, resulting in elevation of the 18:0 FA content in ssi2 plants. Because reduced S-ACP DES activity leads to the induction of certain defense responses and the inhibition of others, we propose that a FA-derived signal modulates crosstalk between different defense signaling pathways.

Amino Acid Sequence↗