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As a multifunctional phytohormone, melatonin (Mel) plays pivotal roles in plant responses to multiple stresses. However, its mechanism of action remains elusive. In the present study, we evaluated the role of NO and Ca2+ signaling in Mel enhanced cold tolerance in winter turnip rape. The results showed that the NO content and concentration of intracellular free Ca2+ ([Ca2+] cyt) increased by 35.42% and 30.87%, respectively, in the leaves of rape seedlings exposed to cold stress. Compared with those of the seedlings in cold stress alone, the NO content and concentration of [Ca2+] cyt in rape seedlings pretreated with Mel increased further. In addition, the Mel-mediated improvement of cold tolerance was inhibited by L-NAME (a NO synthase inhibitor), tungstate (a nitrate reductase inhibitor), LaCl 3 (a Ca2+ channel blocker), and EGTA (a Ca2+ chelator), and this finding was mainly reflected in the increase in ROS content and the decrease in osmoregulatory capacity, photosynthetic efficiency and antioxidant enzyme activities, and expression levels of antioxidant enzyme genes. These findings suggest that NO and Ca2+ are necessary for Mel to improve cold tolerance and function synergistically downstream of Mel. Notably, the co-treatment of Mel with L-NAME, tungstate, LaCl 3 , or EGTA also inhibited the Mel-induced expression of MAPK3/6 under cold stress. In conclusion, NO and Ca2+ are involved in the enhancement of cold tolerance induced by Mel through activating the MAPK cascades in rape seedlings, and a crosstalk may exist between NO and Ca2+ signaling. [Display omitted] • Melatonin (Mel) caused the accumulation of NO and [Ca2+] cyt. • Inhibition of NO and Ca2+ signaling inverted the positive effect of melatonin. • NO, Ca2+ and MAPK cascades participated in melatonin-induced cold tolerance. [ABSTRACT FROM AUTHOR]

This study investigates the effects of γ-Aminobutyric acid (GABA) and mitogen-activated protein kinase (MAPK) inhibitor (PD98059) in disease resistance in red pitaya fruit. Results demonstrated that GABA treatment suppressed the growth of Gilbertella persicaria ; increased H 2 O 2 content and O 2 •- production rate; enhanced reduced glutathione and ascorbic acid contents, as well as increased the activities and transcripts of catalase (CAT), NADPH oxidase (NOX), peroxidise (POD), superoxide dismutase (SOD), ascorbate peroxidase (APX) and glutathione reductase (GR), and up-regulated HcMYB111 / 24 expressions. Furthermore, GABA promoted the expressions of HcMAPKKK1 - HcMAPKK2 / 4 - HcMAPK1 / 7 cascades. However, PD98059 +GABA treatment decreased the disease resistance against G. persicaria and reduced H 2 O 2 content; inhibited the activities and gene expressions of NOX, CAT, SOD, POD, GR and APX, and down-regulated the expressions of HcMAPK1 / 7. These findings suggest that GABA induces disease resistance by regulating ROS metabolism and MAPK cascades in red pitaya fruit. • GABA treatment reduced postharvest disease in red pitaya fruit. • PD98059 +GABA treatment increased disease incidence in red pitaya fruit. • GABA treatment induced ROS homeostasis to enhance disease resistance. • GABA mediated the activation of MAPK cascade to enhance antioxidant systems. [ABSTRACT FROM AUTHOR]

Phenolic acids are the major bioactive metabolites produced in Salvia miltiorrhiza , a traditional Chinese medicine called Danshen. Many phytohormone elicitor treatments induce phenolic acid biosynthesis, even though the underlying mechanism remains obscure. Expression pattern analysis showed that SmMAPK3 was highly expressed in leaves, and SmMAPK3 was significantly induced by salicylic acid (SA) and methyl jasmonate (JA). Bioinformatics analysis revealed that SmMAPK3 belongs to group A and contains a TEY motif in the activation loop together with three conserved regions (P-loop, C-loop and CD-domain). A previous study speculated that SmMAPK3 is likely a positive regulator in the biosynthesis of phenolic acids in S. miltiorrhiza. In this study, overexpression of SmMAPK3 increased phenolic acid biosynthetic gene expression and enhanced the accumulation of phenolic acids in S. miltiorrhiza plantlets. Yeast two-hybrid (Y2H) analysis and firefly luciferase complementation imaging (LCI) assays revealed that SmMAPKK2/4/5/7-SmMAPK3-SmJAZs form a cascade that regulates the accumulation of phenolic acids. In summary, this work deepens our understanding of the posttranscriptional regulatory mechanisms of phenolic acid biosynthesis and sheds new light on metabolic engineering in S. miltiorrhiza. To response the treatment of SA and MeJA, SmMAPK3, the substrate of SmMAPKK2/4/5/7, reduces the stability of transcription repressor SmJAZs/IAAs via phosphorylation and consequently enhances the expression of secondary metabolite genes in S. miltiorrhiza. The SmMAPKK2/4/5/7-SmMAPK3-SmJAZs cascade plays a crucial regulatory role in phenolic acids biosynthesis. [Display omitted] • SmMAPK3 responses to phytohormone SA and MeJA. • Overexpression of SmMAPK3 upregulates phenolic acid biosynthesis. • SmMAPK3 interacts with upstream kinase SmMAPKK2/4/5/7 and downstream transcription repressor JAZs. • The SmMAPKK2/4/5/7-SmMAPK3-SmJAZs cascade regulates secondary metabolism. [ABSTRACT FROM AUTHOR]

Abstract: Mitogen-activated protein kinase (MAPK) cascades are highly conserved signal transduction modules in animals, plants and yeast. MAPK cascades are complicated networks and play vital roles in signal transduction pathways involved in biotic and abiotic stresses. In this study, a maize MAPKK gene, ZmMKK1, was characterized. Quantitative real time PCR (qRT-PCR) analysis demonstrated that ZmMKK1 transcripts were induced by diverse stresses and ABA signal molecule in maize root. Further study showed that the ZmMKK1-overexpressing Arabidopsis enhanced the tolerance to salt and drought stresses. However, seed germination, post-germination growth and stomatal aperture analysis demonstrated that ZmMKK1 overexpression was sensitive to ABA in transgenic Arabidopsis. Molecular genetic analysis revealed that the overexpression of ZmMKK1 in Arabidopsis enhanced the expression of ROS scavenging enzyme- and ABA-related genes, such as POD, CAT, RAB18 and RD29A under salt and drought conditions. In addition, heterologous overexpression of ZmMKK1 in yeast (Saccharomyces cerevisiae) improved the tolerance to salt and drought stresses. These results suggested that ZmMKK1 might act as an ABA- and ROS-dependent protein kinase in positive modulation of salt and drought tolerance. Most importantly, ZmMKK1 interacted with ZmMEKK1 as evidenced by yeast two-hybrid assay, redeeming a deficiency of MAPK interaction partners in maize. [Copyright &y& Elsevier]

Abstract: The ERK cascade is a central signaling pathway that regulates a large number of intracellular processes including proliferation, differentiation, development and also survival or apoptosis. The induction of so many distinct and even opposing cellular processes raises the question as to how the signaling specificity of the cascade is regulated. In the past few years, subcellular localization of components of the ERK cascade was shown to play an important role in specificity determination. Here we describe the dynamic subcellular localization of Raf kinases, MEKs, and particularly ERKs, which translocate into the nucleus during many cellular processes to induce transcription. We also describe in details the recent identification of a novel nuclear translocation mechanism for ERKs, which is based on a nuclear translocation sequence (NTS) within their kinase insert domain (KID). Phosphorylation of this domain, mainly upon stimulation, allows ERKs to interact with the nuclear importing protein – importin7, which mediates the penetration of the interacting ERKs into the nucleus via nuclear pores. Interestingly, the NTS is not specific to ERKs, and seems to be a general signal for regulating nuclear accumulation of various proteins, including MEKs, upon their stimulation. Better understanding of this mechanism may clarify the role of the massive nuclear translocation of many regulatory proteins shortly after their stimulation. [Copyright &y& Elsevier]

Signal transduction pathways in eukaryotic cells integrate diverse extracellular signals, and regulate complex biological responses such as growth, differentiation and death. One group of proline-directed Ser/Thr protein kinases, the mitogen-activated protein kinases (MAPKs), plays a central role in these signalling pathways. Much attention has focused in recent years on three subfamilies of MAPKs, the extracellular signal regulated kinases (ERKs), c-Jun N-terminal kinases (JNKs) and the p38 MAPKs. However, the ERK family is broader than the ERK1 and ERK2 proteins that have been the subject of most studies in this area. Here we overview the work on ERKs 3 to 8, emphasising where possible their biological activities as well as distinctive biochemical properties. It is clear from these studies that these additional ERKs show similarities to ERK1 and ERK2, but with some interesting differences that challenge the paradigm of the archetypical ERK1/2 MAPK pathway. [Copyright &y& Elsevier]

The notions of asymptotic amplitude for signals, and Cauchy gain for input/output systems, and an associated small-gain principle, are introduced. These concepts allow the consideration of systems with multiple, and possibly feedback-dependent, steady states. A Lyapunov-like characterization allows the computation of gains for state-space systems, and the formulation of sufficient conditions insuring the lack of oscillations and chaotic behaviors in a wide variety of cascades and feedback loops. An application in biology (MAPK signaling) is worked out in detail. [Copyright &y& Elsevier]

In humans and animal models, the kidneys and cardiovascular systems are negatively affected by BPA from the environment. It is considered that BPA have some potential estrogen-like and non-hormone-like properties. In this study, RNA-sequencing and its-related bioinformatics was used as the basic strategy to clarify the characteristic mechanisms of kidney–heart axis remodeling and dysfunction in diabetic male rats under BPA exposure. We found that continuous BPA exposure in diabetic rats aggravated renal impairment, and caused hemodynamic disorders and dysfunctions. There were 655 and 125 differentially expressed genes in the kidney and heart, respectively. For the kidneys, functional annotation and enrichment, and gene set enrichment analyses identified bile acid secretion related to lipid synthesis and transport, and MAPK cascade pathways. For the heart, these bioinformatics analyses clearly pointed to MAPKs pathways. A total of 12 genes and another total of 6 genes were identified from the kidney tissue and heart tissue, respectively. Western blotting showed that exposure to BPA activated MAPK cascades in both organs. In this study, the exacerbated remodeling of diabetic kidney–heart axis under BPA exposure and diabetes might occur through hemodynamics, metabolism disorders, and the immune-inflammatory response, as well as continuous estrogen-like stimulation, with focus on the MAPK cascades. [Display omitted] • Environmental BPA exposure accelerated damage to the structures of both organs, aggravated renal impairment, and caused hemodynamic disorders in the status of diabetes mellitus. • The dual effects of chronic BPA exposure and diabetes mellitus were determined to exacerbate kidney–heart axis remodeling characterized by destruction and dysfunction. • The alterations of the axis accelerated by environmental BPA might occur through hemodynamics, metabolism, and the immune-inflammatory response, with focus on the MAPK cascades, and not completely depend on the estrogenic effect of BPA. This study to understand how environmental disrupting chemicals interact with pathologies associated with diabetes is an important topic, and the use of the metabolic disease model to examine the effects of BPA exposure and diabetes on alternations of kidney-heart axis is innovative. [ABSTRACT FROM AUTHOR]

• An anti-periodontitis mixture of tyrosine and lactic acid (3T1L) was identified. • 3T1L abolished bone resorption through RANKL-induced osteoclastogenesis. • 3T1L regulated MAPK signal phosphorylation and NF-κB to improve periodontitis. • NTU101FSMEE has potential to be used as a functional food supplement. Excessive inflammatory response and oxidative stress are the leading causes of periodontal disease (PD). Previously, we reported that Lactobacillus paracasei subsp. paracasei NTU 101-fermented skim milk ethanol extract (NTU101FSMEE) may be useful for developing anti-periodontitis products. In this study, the bioactive ingredient in NTU101FSMEE was isolated and identified as a mixture of tyrosine and lactic acid in 3:1 ratio (3T1L). Treatment of RAW 264.7 and HGF-1 cells with 3T1L significantly reduced the levels of various cytokines participating in the inflammatory response of PD. 3T1L inhibited osteoclastogenesis by decreasing the tartrate-resistant acid phosphatase-related index and suppressed bone resorption by regulating matrix metalloproteinase‐9 and tissue inhibitor of metalloproteinase‐1 levels. Furthermore, 3T1L modulated the intracellular oxidative stress and expression of mitogen-activated protein kinases and the nuclear factor-κB signaling pathway observed in response to lipopolysaccharide. Our findings suggest the potential of 3T1L derived from NTU101FSMEE for anti-periodontitis application. [ABSTRACT FROM AUTHOR]

Summary Mitogen-activated protein kinase cascades are important signaling modules that convert environmental stimuli into cellular responses. We show that MPK3, MPK4, and MPK6 are rapidly activated after cold treatment. The mpk3 and mpk6 mutants display increased expression of CBF genes and enhanced freezing tolerance, whereas constitutive activation of the MKK4/5-MPK3/6 cascade in plants causes reduced expression of CBF genes and hypersensitivity to freezing, suggesting that the MKK4/5-MPK3/6 cascade negatively regulates the cold response. MPK3 and MPK6 can phosphorylate ICE1, a basic-helix-loop-helix transcription factor that regulates the expression of CBF genes, and the phosphorylation promotes the degradation of ICE1. Interestingly, the MEKK1-MKK2-MPK4 pathway constitutively suppresses MPK3 and MPK6 activities and has a positive role in the cold response. Furthermore, the MAPKKK YDA and two calcium/calmodulin-regulated receptor-like kinases, CRLK1 and CRLK2, negatively modulate the cold activation of MPK3/6. Our results uncover important roles of MAPK cascades in the regulation of plant cold response. [ABSTRACT FROM AUTHOR]