Search Results (140)

Protein kinases and phosphatases are essential for post-translational regulation, enabling bacteria to adapt to environmental stresses and modulate virulence. While prior reviews have broadly covered their roles in stress response, antibiotic resistance, and virulence, this article updates specifically on the roles of histidine kinases (HKs) and serine/threonine kinases (STKs) in mediating phage-bacteria interactions. A key aspect is phage-encoded kinases, which hijack bacterial signalling by phosphorylating and disrupting host processes to promote infection. Despite their importance, significant gaps remain in understanding these regulatory networks. This microreview highlights both the unresolved mechanisms and the therapeutic potential of targeting kinase pathways—for instance, by disrupting phage evasion strategies or enhancing phage-based antimicrobial therapies. Full article

Rootstocks largely determine the tree architecture of the grafted scions, significantly affects yield, suitability for mechanical harvesting, and planting pattern of apple orchards. It is thus important to reveal the mechanisms behind the rootstocks influence on the tree architecture of scions in apple trees. This study analyzed the grafting survival rate, the physiological parameters including plant growth, photosynthesis and nutrient accumulation in the apple variety ‘Harlikar’ with eight apple rootstocks. We also explored the mechanism of scion architecture formation using transcriptomics based on different scion/rootstock combinations. The results indicated that ‘Harlikar’ had the lowest grafting survival rate with rootstock ‘M26’, with less callus formed at the graft interface, foliage etiolation, and weak photosynthetic capacity. While ‘Harlikar’ had better affinities with ‘M9-T337’, ‘M9-Nic29’, ‘M9-Pajam2’, ‘B9’, ‘71-3-150’, ‘Qingzhen 2’, and ‘Malus baccata’. Among these, the highest plant height and the highest number of lateral branches were observed in ‘Harlikar’ with rootstock ‘Qingzhen 2’, they were 1.12-times and 2.0-times higher than ‘Harlikar’ with vigorous rootstock ‘M. baccata’, respectively. The highest accumulations of total nitrogen, total phosphorus, and total potassium in scions were observed in ‘Harlikar’/‘Qingzhen 2’, they were 2.22-times, 2.10-times, and 11.80-times higher than that in ‘Harlikar’/‘M. baccata’. The lowest plant height was observed in ‘Harlikar’/‘71-3-150’, only 50.47% of ‘Harlikar’/‘Qingzhen 2’ and 56.51% of ‘Harlikar’/‘M. baccata’, and the lowest internode length was observed in ‘Harlikar’/‘M9-Nic29’, only 60.76% of ‘Harlikar’/‘Qingzhen 2’ and 79.11% of ‘Harlikar’/‘M. baccata’. The transcriptome, weighted gene co-expression network and KEGG enrichment analyses revealed that, compared to ‘Harlikar’/‘M. baccata’, most differentially expressed genes screened from ‘Harlikar’/‘Qingzhen 2’, ‘Harlikar’/‘71-3-150’, and ‘Harlikar’/‘M9-Nic29’ were enriched in hormone signal transduction pathways. Specifically, auxin-repressed protein gene ARP, cytokinin synthesis related genes CKXs and CYP92A6, and brassinosteroid synthesis related gene CYP87A3 were involved in the dwarfing of ‘Harlikar’/‘71-3-150’ and ‘Harlikar’/‘M9-Nic29’. Cytokinin synthesis related gene ARR-A and abscisic acid-responsive element binding factor gene ABF were the key to increased branching in ‘Harlikar’/‘Qingzhen 2’. In addition, acid phosphatase genes ACPs, and serine/threonine-protein kinase genes PBLs were involved in the vegetative growth of scions in ‘Harlikar’/‘Qingzhen 2’ by affecting the absorption and utilization of nutrients. These results provide theoretical guidance for cultivating high-quality ‘Harlikar’ apple trees and elucidate the molecular mechanisms regulating plant height and lateral branch formation in apple. Full article

Background: Houge-Janssens syndrome 1 is a condition with onset in early childhood caused by heterozygous pathogenic variants in the PPP2R5D gene, which encodes a B56 regulatory subunit of the serine/threonine protein phosphatase 2A (PP2A). There is evidence that the PP2A-PPP2R5D complex is involved in regulating the phosphatidylinositol 3-kinase (PI3K)/AKT signalling pathway, which is crucial for several cellular processes, including the pathogenesis and progression of haemangiomas. Case presentation: We report the first PPP2R5D-related neurodevelopmental disorder case from Sardinia, a child with transient hypoglycaemia, facial dysmorphisms, and multiple haemangiomas. Whole Exome Sequencing analysis confirmed the clinical suspicion, detecting the presence of the de novo missense variant c.592G>A in the PPP2R5D gene. Conclusions: Haemangiomas have never been linked to the syndromic phenotype of the PPP2R5D-associated disorder. The close correlation between the PP2A enzyme and the PI3K/AKT signalling pathway suggests the possible correlation between its dysfunction and activation of haemangiogenesis. Our report highlights a possible link between the PPP2R5D-related disorder and altered angiogenesis, characterizing diffuse haemangiomas as a possible novel phenotypic trait of this condition. Full article

In light of the increasingly adverse environmental conditions and the concomitant challenges to the survival of important crops, there is a pressing need to enhance the resilience of pepper seedlings to extreme weather. Carotenoid plays an important role in plants’ resistance to abiotic stress. Nevertheless, the relationship between carotenoid biosynthesis and sweet pepper seedlings’ resistance to different abiotic stresses remains uncertain. In this study, the carotenoid content in abiotic-stressed sweet pepper seedling roots was determined, revealing that carotenoid content was extremely significantly elevated by more than 16-fold under salt stress, followed by drought stress (8-fold), and slightly elevated by only about 1-fold under waterlogging stress. After that, serine/threonine-protein phosphatase 2A (PP2A) was found to be the suitable reference gene (RG) in sweet pepper seedling roots under different abiotic stresses by using RT-qPCR and RefFinder analysis. Subsequently, using PP2A as the RG, RT-qPCR analysis showed that the expression level of most genes associated with carotenoid biosynthesis was extremely significantly up-regulated in sweet pepper seedlings under salt and drought stress. Specifically, violoxanthin deepoxidase (VDE) was significantly up-regulated by more than 481- and 36-fold under salt and drought stress, respectively; lycopene epsilon cyclase (LCYE) was significantly up-regulated by more than 840- and 23-fold under salt and drought stress, respectively. This study contributes to a more comprehensive understanding of the carotenoid biosynthesis pathway serving as a major source of retrograde signals in pepper subjected to different abiotic stresses. Full article

Melanomas, which develop on malignant transformations of melanocytes, are highly malignant and prone to metastasis; therefore, effective drugs are required. The Momordica charantia (MC) extract has been shown to suppress cancer cell proliferation and invasion; however, the effect of the MC extract on melanoma in living organisms remains unclear. In this study, we investigated the mechanism underlying the amelioration of melanoma cell extravasation into mouse lungs by the MC extract. Male C57BL/6j mice (aged 8 weeks) were injected with B16 melanoma cells (1 × 10⁵ cells/mouse). Subsequently, they were orally administered the MC extract daily for 2 weeks; mouse lung samples were obtained on the final day and analyzed. The MC extract ameliorated melanoma proliferation and infiltration into the lungs caused by melanoma cell treatment. It also increased phosphatase and tensin homolog deletion from chromosome 10 and suppressed paired box gene 3 (PAX3) and the phosphatidylinositol trisphosphate/RAC-alpha serine/threonine-protein kinase/mammalian target of rapamycin complex 1 signaling. Furthermore, it decreased microphthalmia-associated transcription factors and induced the suppression of cyclin-dependent kinase 2, hepatocyte growth factor receptor, B-cell/CLL lymphoma 2, and Ras-related proteins. Our findings suggest that the MC extract suppresses tumor survival genes by regulating PAX3, thereby ameliorating melanoma proliferation and invasion. Full article

Reversible protein phosphorylation, known as the “switch” of the cell, is controlled by protein kinases (PKs) and protein phosphatases (PPs). Based on substrate specificity, PPs are classified into protein serine/threonine phosphatases and protein tyrosine phosphatases (PTPs). PTPs can dephosphorylate phosphotyrosine and phosphoserine/phosphothreonine. In plants, PTPs monitor plant physiology, growth, and development. This review summarizes an overview of the PTPs’ classification and describes how PTPs regulate various plant processes, including plant growth and development, plant hormone responses, and responses to abiotic and biotic stresses. Then, future research directions on the PTP family in plants are discussed. This summary will serve as a reference for researchers studying PTPs in plants. Full article

Alkaline water is toxic to cultured aquatic animals that frequently live in pH-neutral freshwater. Overfishing and habitat destruction have contributed to the decline in the wild sturgeon population; consequently, the domestic hybrid sturgeon has become an increasingly important commercial species in China. Hybrid sturgeons are widely cultured in alkaline water, but little is known about the effects of alkalinity stress on hybrid sturgeon liver tissues. We exposed hybrid sturgeons to four alkaline concentrations (3.14 ± 0.02 mmol/L, 7.57 ± 0.08 mmol/L, 11.78 ± 0.24 mmol/L and 15.46 ± 0.48 mmol/L). Histopathology, biochemical index assessment, gene expression level detection and metabolomics analysis were used to investigate the negative effects on liver functions following exposure to NaHCO₃. Livers exposed to alkaline stress exhibited severe tissue injury and clear apoptotic characteristics. With increased exposure concentrations, the hepatic superoxide dismutase, catalase, glutathione peroxidase and alkaline phosphatase activities significantly decreased in a dose-dependent manner. NaHCO₃ exposure up-regulated the transcriptional levels of apoptosis/ferroptosis-related genes in livers. Similarly, the expression trends of interleukin-1β and heat shock protein genes also increased in high-alkalinity environments. However, the expression levels of complement protein 3 significantly decreased (p < 0.05). Hepatic untargeted metabolomics revealed the alteration conditions of various metabolites associated with the antioxidant response, the ferroptosis process and amino acid metabolism (such as beta-alanine metabolism; alanine, aspartate and glutamate metabolism; and glycine, serine and threonine metabolism). These data provided evidence that NaHCO₃ impaired immune functions and the integrity of hybrid sturgeon liver tissues by mediating oxidative-stress-mediated apoptosis and ferroptosis. Our results shed light on the breeding welfare of domestic hybrid sturgeons and promote the economic development of fisheries in China. Full article

The Tam Giang-Cau Hai lagoon (TGCH) in Thua Thien Hue province (Vietnam) is a marsh/lagoon system and ranks among the largest waterbodies in Southeast Asia. It plays a significant role in terms of both socio-economic and environmental resources. However, anthropogenic stress, as well as the discharge of untreated domestic and industrial sewage with agricultural runoff from its three major tributaries, dramatically damages the water quality of the lagoon. Especially after heavy rain and flash floods, the continuous degradation of its water quality, followed by harmful algal and cyanobacterial bloom patterns (HABs), is more perceptible. In this study, several physicochemical factors, cyanotoxins (anatoxins (ATXs), saxitoxins (STXs), microcystins (MCs)), phycotoxins (STXs, okadaic acid (OA), and dinophysistoxins (DTXs)) were analyzed in water and shellfish samples from 13 stations in June 2023 from 13 stations, using enzyme-linked immunosorbent assay (ELISA) kits for the ATXs and STXs, and the serine/threonine phosphatase type 2A (PP2A) inhibition assay kit for the MCs, OA, and DTXs. The results showed for the first time the co-occurrence of freshwater cyanotoxins and marine phycotoxins in water and shellfish samples in this lagoon. Traces of ATXs and STXs were detected in the shellfish and the orders of magnitude were below the seafood safety action levels. However, toxins inhibiting the PP2A enzyme, such as MCs and nodularin (NODs), as well as OA and DTXs, were detected at higher concentrations (maximum: 130.4 μg equiv. MC-LR/kg shellfish meat wet weight), approaching the actionable level proposed for this class of toxin in shellfish (160 μg of OA equivalent per kg of edible bivalve mollusk meat). It is very important to note that due to the possible false positives produced by the ELISA test in complex matrices such as a crude shellfish extract, this preliminary and pilot research will be repeated with a more sophisticated method, such as liquid chromatography coupled with mass spectroscopy (LC-MS), in the upcoming research plan. Full article

Sugar beet is an important sugar crop, and its roots are mainly used for processing raw materials to produce products such as sugar, molasses, and saccharin, as well as being used as fodder for livestock. BvCPD, a key enzyme gene for brassinosteroid (BR) synthesis, regulates the development of parenchyma cells and vascular bundles by promoting BR synthesis, which promotes the expansion of the sugar beet taproot and influences the growth, development, and yield of sugar beets. This study investigated the impact of BvCPD on the physiological metabolism of sugar beet utilizing BvCPD overexpression, silent, and wild-type (WT) lines. BvCPD increased the chlorophyll content and maximum photochemical efficiency and improved the photosynthetic characteristics of sugar beet leaves. Simultaneously, BvCPD increased the rate of sugar beet taproot respiration and ATP content by enhancing the activities of phosphoglycerate kinase, alcohol dehydrogenase, sucrose synthase, and sucrose synthase catabolism. Moreover, BvCPD induced changes in the sugar fraction content, which increased the sugar yield of a single plant. In addition, BvCPD promoted water absorption, nitrogen accumulation, and lignin/cellulose synthesis activities, facilitated by increased activities of phenylalanine ammonia-lyase, cinnamyl alcohol dehydrogenase, cellulose synthase, and protein serine/threonine phosphatases, providing the requisite energy and materials for sugar beet growth. These findings not only provide a new perspective for understanding the physiological mechanisms regulating the growth of sugar beets but also provide a theoretical basis for the future improvement of sugar beet varieties through molecular breeding techniques. Full article

Tumor angiogenesis, the formation of new blood vessels to support tumor growth and metastasis, is a complex process regulated by a multitude of signaling pathways. Dysregulation of signaling pathways involving protein kinases has been extensively studied, but the role of protein phosphatases in angiogenesis within the tumor microenvironment remains less explored. However, among angiogenic pathways, protein phosphatases play critical roles in modulating signaling cascades. This review provides a comprehensive overview of the involvement of protein phosphatases in tumor angiogenesis, highlighting their diverse functions and mechanisms of action. Protein phosphatases are key regulators of cellular signaling pathways by catalyzing the dephosphorylation of proteins, thereby modulating their activity and function. This review aims to assess the activity of the protein tyrosine phosphatases and serine/threonine phosphatases. These phosphatases exert their effects on angiogenic signaling pathways through various mechanisms, including direct dephosphorylation of angiogenic receptors and downstream signaling molecules. Moreover, protein phosphatases also crosstalk with other signaling pathways involved in angiogenesis, further emphasizing their significance in regulating tumor vascularization, including endothelial cell survival, sprouting, and vessel maturation. In conclusion, this review underscores the pivotal role of protein phosphatases in tumor angiogenesis and accentuate their potential as therapeutic targets for anti-angiogenic therapy in cancer. Full article

Proso millet (Panicum miliaceum L.) is resilient to abiotic stress, especially to drought. However, the mechanisms by which its roots adapt and tolerate salt stress are obscure. In this study, to clarify the molecular mechanism of proso millet in response to drought stress, the physiological indexes and transcriptome in the root of seedlings of the proso millet cultivar ‘Yumi 2’ were analyzed at 0, 0.5, 1.0, 1.5, and 3.0 h of stimulated drought stress by using 20% PEG-6000 and after 24 h of rehydration. The results showed that the SOD activity, POD activity, soluble protein content, MDA, and O₂⁻· content of ‘Yumi 2’ increased with the time of drought stress, but rapidly decreased after rehydration. Here, 130.46 Gb of clean data from 18 samples were obtained, and the Q30 value of each sample exceeded 92%. Compared with 0 h, the number of differentially expressed genes (DEGs) reached the maximum of 16,105 after 3 h of drought, including 9153 upregulated DEGs and 6952 downregulated DEGs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that upregulated DEGs were mainly involved in ATP binding, nucleus, protein serine/threonine phosphatase activity, MAPK signaling pathway–plant, plant–pathogen interactions, and plant hormone signal transduction under drought stress, while downregulated DEGs were mainly involved in metal ion binding, transmembrane transporter activity, and phenylpropanoid biosynthesis. Additionally, 1441 TFs screened from DEGs were clustered into 64 TF families, such as AP2/ERF-ERF, bHLH, WRKY, NAC, MYB, and bZIP TF families. Genes related to physiological traits were closely related to starch and sucrose metabolism, phenylpropanoid biosynthesis, glutathione metabolism, and plant hormone signal transduction. In conclusion, the active oxygen metabolism system and the soluble protein of proso millet root could be regulated by the activity of protein serine/threonine phosphatase. AP2/ERF-ERF, bHLH, WRKY, NAC, MYB, and bZIP TF families were found to be closely associated with drought tolerance in proso millet root. This study will provide data to support a subsequent study on the function of the drought tolerance gene in proso millet. Full article

Pediatric neuroblastomas (NBs) are heterogeneous, aggressive, therapy-resistant embryonal tumors that originate from cells of neural crest origin committed to the sympathoadrenal progenitor cell lineage. Stress- and drug-resistance mechanisms drive post-therapeutic relapse and metastatic progression, the characterization and inhibition of which are major goals in improving therapeutic responses. Stress- and drug-resistance mechanisms in NBs include alternative TrkAIII splicing of the neurotrophin receptor tropomyosin-related kinase A (NTRK1/TrkA), which correlates with post-therapeutic relapse and advanced-stage metastatic disease. The TrkAIII receptor variant exerts oncogenic activity in NB models by mechanisms that include stress-induced mitochondrial importation and activation. In this study, we characterize novel targetable and non-targetable participants in this pro-survival mechanism in TrkAIII-expressing SH-SY5Y NB cells, using dithiothreitol (DTT) as an activator and a variety of inhibitors by regular and immunoprecipitation Western blotting of purified mitochondria and IncuCyte cytotoxicity assays. We report that stress-induced TrkAIII misfolding initiates this mechanism, resulting in Grp78, Ca²⁺-calmodulin, adenosine ribosylating factor (Arf) and Hsp90-regulated mitochondrial importation. TrkAIII imported into inner mitochondrial membranes is cleaved by Omi/high temperature requirement protein A2 (HtrA2) then activated by a mechanism dependent upon calmodulin kinase II (CaMKII), alpha serine/threonine kinase (Akt), mitochondrial Ca²⁺ uniporter and reactive oxygen species (ROS), involving inhibitory mitochondrial protein tyrosine phosphatase (PTPase) oxidation, resulting in phosphoinositide 3 kinase (PI3K) activation of mitochondrial Akt, which enhances stress resistance. This novel pro-survival function for misfolded TrkAIII mitigates the cytotoxicity of mitochondrial Ca²⁺ homeostasis disrupted during integrated stress responses, and is prevented by clinically approved Trk and Akt inhibitors and also by inhibitors of 78kDa glucose regulated protein (Grp78), heat shock protein 90 (Hsp90), Ca²⁺-calmodulin and PI3K. This identifies Grp78, Ca²⁺-calmodulin, Hsp90, PI3K and Akt as novel targetable participants in this mechanism, in addition to TrkAIII, the inhibition of which has the potential to enhance the stress-induced elimination of TrkAIII-expressing NB cells, with the potential to improve therapeutic outcomes in NBs that exhibit TrkAIII expression and activation. Full article

Protein serine/threonine phosphatase 2A (PP2A) regulates diverse cellular processes via the formation of ~100 heterotrimeric holoenzymes. However, a scarcity of knowledge on substrate recognition by various PP2A holoenzymes has greatly prevented the deciphering of PP2A function in phosphorylation-mediated signaling in eukaryotes. The review summarized the contribution of B56 phosphorylation to PP2A-B56 function and proposed strategies for intervening B56 phosphorylation to treat diseases associated with PP2A-B56 dysfunction; it especially analyzed recent advancements in LxxIxEx B56-binding motifs that provide the molecular details of PP2A-B56 binding specificity and, on this basis, explored the emerging role of PP2A-B56 in the mitosis process, virus attack, and cancer development through LxxIxE motif-mediated PP2A-B56 targeting. This review provides theoretical support for discriminatingly targeting specific PP2A holoenzymes to guide PP2A activity against specific pathogenic drivers. Full article

This review summarizes our research on nicotinic acetylcholine receptors in human chromaffin cells. Limited research has been conducted in this field on human tissue, primarily due to the difficulties associated with obtaining human cells. Receptor subtypes were characterized here using molecular biology and electrophysiological patch-clamp techniques. However, the most significant aspect of this study refers to the cross-talk between the two main subtypes identified in these cells, the α7- and α3β4* subtypes, aiming to avoid their desensitization. The article also reviews other aspects, including the regulation of their expression, function or physical interaction by choline, Ca²⁺, and tyrosine and serine/threonine phosphatases. Additionally, the influence of sex on their expression is also discussed. Full article

The dual leucine zipper kinase (DLK) alias mitogen-activated protein 3 kinase 12 (MAP3K12) has gained much attention in recent years. DLK belongs to the mixed lineage kinases, characterized by homology to serine/threonine and tyrosine kinase, but exerts serine/threonine kinase activity. DLK has been implicated in many diseases, including several neurodegenerative diseases, glaucoma, and diabetes mellitus. As a MAP3K, it is generally assumed that DLK becomes phosphorylated and activated by upstream signals and phosphorylates and activates itself, the downstream serine/threonine MAP2K, and, ultimately, MAPK. In addition, other mechanisms such as protein–protein interactions, proteasomal degradation, dephosphorylation by various phosphatases, palmitoylation, and subcellular localization have been shown to be involved in the regulation of DLK activity or its fine-tuning. In the present review, the diverse mechanisms regulating DLK activity will be summarized to provide better insights into DLK action and, possibly, new targets to modulate DLK function. Full article