Aug 2026· Plant physiology and biochemistry : PPB· Vol 238, pp.
111613
· 0 citations· 78 references
Medicine
TL;DR
It is found that roots of loss-of-function mutants of several MAPK cascade components exhibited significantly reduced responsiveness to eATP compared with the wild type, demonstrating that the MAPK cascade may serve as a crucial signaling module in eATP-regulated root growth in Arabidopsis thaliana.
Abstract
The mitogen-activated protein kinase (MAPK) cascades play vital roles in mediating plant cell responses to external stimuli by regulating intracellular metabolism. We have previously reported that extracellular ATP (eATP) acts as an apoplastic messenger to regulate root growth, and that two receptor-like kinases, LRK10L3 and BAK1, play essential roles in this process. However, the intracellular signaling mechanisms through which eATP influences root growth remain unclear. In this study, we found that roots of loss-of-function mutants of several MAPK cascade components exhibited significantly reduced responsiveness to eATP compared with the wild type. eATP stimulated the expression of genes encoding MAPK cascade components, and in several upstream-element null mutants, eATP-induced expression of downstream members was enhanced. Moreover, eATP increased the phosphorylation of MAPK cascade components, suggesting that a cascade comprising MEKK1/YDA-MKK4/5-MPK3/6 is involved in the response of root cells to eATP. eATP may activate this MAPK cascade via LRK10L3 and BAK1, because eATP-stimulated phosphorylation of MEKK1 and YDA was impaired in double-null mutants lacking both receptor-like kinases. eATP also induced the translocation of MKK4/5 and MPK3/6 from the cytoplasm to the nucleus, a process partially dependent on phosphorylation. In mutants lacking functional MAPKs, eATP-stimulated expression of several jasmonic acid (JA) biosynthesis-related genes was compromised. Collectively, these results demonstrate that the MAPK cascade may serve as a crucial signaling module in eATP-regulated root growth in Arabidopsis thaliana, providing insights for further investigation of eATP signaling mechanisms.
ABSTRACT Phosphorylation, carried out by kinases, is a pivotal mechanism for all cell signal transduction pathways. In eukaryotic cells, Mitogen-Activated Protein Kinases (MAPK) form modules with three kinases (MAPKKK, MAPKK, and MAPK) that are sequentially activated, participating in multiple signaling mechanisms. The second kinase forming a typical module is called MAP kinase kinase (MAPKK or MKK), which receives the signal from MAPKKK and transmits it to MAPK. The Arabidopsis thaliana genome has 10 MKKs and they are classified into four different groups (A, B, C, and D). To date, several aspects of the MKK functioning are known, but there is little information about MKK expression in plant tissues. Here, each MKK upstream region was fused to the UidA reporter, and these pMKK1-10:UidA constructions were used to reveal the MKK expression patterns in the tissues of the seedlings during their early development. This experimental expression analysis was complemented with a detailed bioinformatic analysis focused on identifying the cis-regulatory elements present in these upstream promoter regions.
Salvador Barrera-Ortiz, J. M. González-Coronel, Yessica Casales-Tlatilpa et al.· Plant Signalling & Behavior· 0 citations
The main axis of the plant body is established in early embryogenesis. Polar growth and asymmetric division of the Arabidopsis zygote require the Mitogen-Activated Protein (MAP) kinase kinase kinase YODA and the MAP kinases MPK3/MPK6, but regulation of this signaling cascade is not well understood. Here, we show that three BSU1-LIKE phosphatases (BSL1-3) are essential positive regulators: A combined loss causes closely similar defects to loss of the YODA MAP kinase cascade, resulting in nonpolar embryos; transcriptional profiling and cell-fate markers confirm that BSL phosphatases and the MAP kinase cascade regulate the same process. Unexpectedly, the founding member of the family, BSU1, appears dispensable. These results cast doubt on the view of BSU1-family phosphatases as core components of brassinosteroid hormone signaling. MPK3 activity shows striking sensitivity to BSL dosage, and genetic interactions with activated MPK3 suggest that BSL phosphatases function downstream of YODA and either in conjunction with or downstream of MPK3/MPK6, implying a novel mechanism of MPK regulation.
Sangho Jeong, Gabriel Eschedor, Magdy S. Alabady et al.· Proceedings of the National...· 1 citation
ABSTRACT The downstream effectors that mediate the pro‑viral function of the MAPK pathway during enterovirus 71 (EV71) infection remain poorly defined. Here we show that early growth response 1 (EGR1) is independently regulated by each of the three classical MAPK branches including extracellular signal-regulated kinase (ERK), p38 and c-Jun N-terminal kinase (JNK), and serves as a common downstream target of these pathways to promote EV71 replication and virus-induced cell death. Furthermore, we found that the natural isoflavone calycosin (CA) from Astragalus membranaceus acts as a regulatory probe of the MAPK-EGR1 axis. CA suppresses EV71-induced expression and phosphorylation of ERK, p38, and JNK, as well as the subsequent upregulation of EGR1, thereby inhibiting both viral replication and virus-induced cell death in conventional cell lines and human colonic organoid infection models. This pro-viral axis is conserved among several enteroviruses, including coxsackievirus B3 and enterovirus D68, and CA exhibits broad-spectrum activity against multiple enteroviruses by targeting this axis. Collectively, our findings establish the MAPK‑EGR1 axis as a key host‑dependency node for EV71 and other enteroviruses, and identify CA as a valuable chemical probe for interrogating this axis. This work not only deepens our understanding of the interplay between enteroviruses such as EV71 and their host, but also provides a mechanistic basis for host‑directed antiviral strategies.
Background The MAPK signalling network coordinates opposing cell fates — proliferation versus apoptosis — by combining the activities of ERK, JNK, and p38 kinases in patterns that depend on upstream MAP3K identity. Using multiplexed kinase translocation reporter (KTR) biosensors and functional assays in MCF10A mammary epithelial cells, Peterson et al. (Cell Systems, 2023) demonstrated that MAP3Ks co-activating ERK and JNK drive approximately tenfold more cell cycle entry than MAP3Ks activating ERK alone, and that both kinase activities are independently required for this proliferative response. The transcriptional mechanism underlying this quantitative difference was not identified in the original study. Results We performed a systematic computational re-analysis of the RNA-seq data deposited by Peterson et al. (GEO: GSE213882), encompassing thirteen MAP3K perturbations in doxycycline-induced MCF10A mammary epithelial cells. Based on signalling responses reported by Peterson et al., MAP3Ks were grouped into ERK-only (RAF1, COT) or ERK+JNK co-activating kinases (MLK1, MLK3, ZAK, TAK1, MEKK2, MEKK3). This stratification identified JNK co-activation as the feature most strongly associated with E2F/MYC transcriptional polarity. ERK-only MAP3Ks showed negative enrichment of E2F TARGETS, G2M CHECKPOINT, and MYC TARGETS Hallmark gene sets, whereas ERK+JNK MAP3Ks showed positive enrichment (each MAP3K individually FDR < 0.05 by GSEA). Consistently, inferred activities of E2F1, E2F2, E2F4, and MYC shifted from negative mean ULM t-scores in the ERK group to strongly positive values in the ERK+JNK group (FDR < 0.05 using the CollecTRI regulon). The observed E2F/MYC polarity was robust to alternative transcription factor inference strategies, being reproduced using the DoRothEA A+B regulon and the multivariate model (MLM) framework (Pearson r = 0.77). The signal remained stable under leave-one-out sensitivity analysis and was independently reproduced in MAP3K overexpression signatures from the LINCS L1000 atlas (GEO: GSE92742). Conclusions ERK activation alone was associated with repression of E2F/MYC transcriptional programmes, whereas JNK co-activation was associated with their activation. These opposing transcriptional states provide a potential explanation for the ∼10-fold differences in cell cycle entry reported by Peterson et al. and supports a model in which pRb/E2F regulation integrates combinatorial MAPK co-activation states beyond the canonical ERK–cyclin D–CDK4/6 axis.
M. Solé, Beatriz Candás-Estébanez, R. K. da Palma et al.· bioRxiv· 0 citations
Cellular adaption to glucose availability requires precise coordination between signaling pathways and gene expression. In Saccharomyces cerevisiae, the vacuole serves as a metabolic hub whose protein composition and activity are dynamically regulated to nutrient availability. Additionally, the Protein Kinase A (PKA) pathway is a central mediator of glucose stress response, acting through the transcriptional factor Msn2. However, how PKA-Msn2 axis connects environmental cues to vacuolar gene expression remains poorly understood.
In this study, we investigate how PKA regulates Msn2 subcellular localization and its impact on expression of PRC1, a representative vacuolar lumenal hydrolase. By combining Msn2 subcellular localization and gene expression analysis, we found glucose limitation induces PRC1 expression, which reduced after deletion of Msn2/4 and disruption of Stress Response Elements (STRE) in PRC1 promoter. Furthermore, reduced PKA activity is associated with nuclear accumulation of Msn2 and enhanced PRC1 expression, whereas deletion of Msn2/4 attenuates this effect. Results reveal that PKA-mediated regulation of Msn2 is essential for glucose stress responses and provide insight into how signaling pathways control PRC1 expression in yeast.
MKK2 mediates the phosphorylation of the Mkc1 MAPK in response to cell wall assembly interfering agents such as zymolyase or tunicamycin and also to oxidative stress and it is shown here that Mkk2 mediates the phosphorylation of the Mkc1 MAPK under different stress conditions.
E. Román, R. Alonso-Monge, Alberto Miranda et al.· 0 citations
