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Biomolecules May 2022Phosphorylation facilitates the regulation of all fundamental biological processes, which has triggered extensive research of protein kinases and their roles in human... (Review)
Review
Phosphorylation facilitates the regulation of all fundamental biological processes, which has triggered extensive research of protein kinases and their roles in human health and disease. In addition to their phosphotransferase activity, certain kinases have evolved to adopt additional catalytic functions, while others have completely lost all catalytic activity. We searched the Universal Protein Resource Knowledgebase (UniProtKB) database for bifunctional protein kinases and focused on kinases that are critical for bacterial and human cellular homeostasis. These kinases engage in diverse functional roles, ranging from environmental sensing and metabolic regulation to immune-host defense and cell cycle control. Herein, we describe their dual catalytic activities and how they contribute to disease pathogenesis.
Topics: Humans; Knowledge Bases; Phosphorylation; Protein Kinases
PubMed: 35625613
DOI: 10.3390/biom12050685 -
Current Opinion in Plant Biology Oct 2020Organisms need to constantly inform their cellular machinery about the biochemical and physical status of their surroundings to adapt and thrive. While some external... (Review)
Review
Organisms need to constantly inform their cellular machinery about the biochemical and physical status of their surroundings to adapt and thrive. While some external signals are also sensed intracellularly, a considerable share of external information is registered already at the plasma membrane (PM). Receptor kinases (RKs) are crucial for plant cells to integrate such cues from the environment, from microbes, or from other cells to coordinate their physiological response and their development. Early studies on RK signaling depicted the path from external signal to internal response in a linear fashion, but recent findings show that these cellular information highways are highly interconnected and pass signals through molecular intersections. In this review, we first discuss how individual RKs simultaneously contribute to the transduction and deconvolution of a multitude of signals by controlled assembly into diverse RK complexes, exemplified by FERONIA signaling versatility. We then elaborate on how cells can exert highly localized control over the assembly, interaction and composition of such complexes in order to attain essential cellular output specificity.
Topics: Carrier Proteins; Cell Membrane; Phosphotransferases; Signal Transduction
PubMed: 32623322
DOI: 10.1016/j.pbi.2020.05.010 -
Molecular Plant May 2024The phytohormone auxin plays a pivotal role in governing plant growth and development. Although the TRANSPORT INHIBITOR RESPONSE1/AUXIN SIGNALING F-BOX (TIR1/AFB)...
The phytohormone auxin plays a pivotal role in governing plant growth and development. Although the TRANSPORT INHIBITOR RESPONSE1/AUXIN SIGNALING F-BOX (TIR1/AFB) receptors function in both the nucleus and cytoplasm, the mechanism governing the distribution of TIR1/AFBs between these cellular compartments remains unknown. In this study, we demonstrate that auxin-mediated oxidation of TIR1/AFB2 is essential for their targeting to the nucleus. We showed that small active molecules, reactive oxygen species (ROS) and nitric oxide (NO), are indispensable for the nucleo-cytoplasmic distribution of TIR1/AFB2 in trichoblasts and root hairs. Further studies revealed that this process is regulated by the FERONIA receptor kinase-NADPH oxidase signaling pathway. Interestingly, ROS and NO initiate oxidative modifications in TIR1 and AFB2, facilitating their subsequent nuclear import. The oxidized forms of TIR1 and AFB2 play a crucial role in enhancing the function of TIR1 and AFB2 in transcriptional auxin responses. Collectively, our study reveals a novel mechanism by which auxin stimulates the transport of TIR1/AFB2 from the cytoplasm to the nucleus, orchestrated by the FERONIA-ROS signaling pathway.
Topics: Arabidopsis; Arabidopsis Proteins; Cell Nucleus; F-Box Proteins; Gene Expression Regulation, Plant; Indoleacetic Acids; Nitric Oxide; Oxidation-Reduction; Phosphotransferases; Protein Serine-Threonine Kinases; Reactive Oxygen Species; Receptors, Cell Surface; Signal Transduction
PubMed: 38581129
DOI: 10.1016/j.molp.2024.04.002 -
The Plant Journal : For Cell and... Nov 2020Root nutation indicates the behavior that roots grow in a waving and skewing way due to unequal growth rates on different sides. Although a few developmental and...
Root nutation indicates the behavior that roots grow in a waving and skewing way due to unequal growth rates on different sides. Although a few developmental and environmental factors have been reported, genetic pathways mediating this process are obscure. We report here that the Arabidopsis CrRLK1L family member FERONIA (FER) is critical for root nutation. Functional loss of FER resulted in enhanced root waviness on tilted plates or roots forming anti-clockwise coils on horizontal plates. Suppressing polar auxin transport, either by pharmacological treatment or by introducing mutations at PIN-FORMED2 (PIN2) or AUXIN RESISTANT1 (AUX1), suppressed the asymmetric root growth (ARG) in fer-4, a null mutant of FER, indicating that FER suppression of ARG depends on polar auxin transport. We further showed by pharmacological treatments that dynamic microtubule organization and Ca signaling are both critical for FER-mediated ARG. Results presented here demonstrate a key role of FER in mediating root nutating growth, through PIN2- and AUX1-mediated auxin transport, through dynamic microtubule organization, and through Ca signaling.
Topics: Arabidopsis; Arabidopsis Proteins; Biological Transport; Calcium Signaling; Indoleacetic Acids; Microtubules; Mutation; Phosphotransferases; Plant Growth Regulators; Signal Transduction
PubMed: 32891072
DOI: 10.1111/tpj.14984 -
Cellular and Molecular Gastroenterology... 2022
Topics: Phosphotransferases (Alcohol Group Acceptor); Homeostasis; Gastrointestinal Tract
PubMed: 36162437
DOI: 10.1016/j.jcmgh.2022.09.001 -
Functional Plant Biology : FPB Jun 2020Rapid response of uni- and multicellular organisms to environmental changes and their own growth is achieved through a series of molecular mechanisms, often involving... (Review)
Review
Rapid response of uni- and multicellular organisms to environmental changes and their own growth is achieved through a series of molecular mechanisms, often involving modification of macromolecules, including nucleic acids, proteins and lipids. The ADP-ribosylation process has ability to modify these different macromolecules in cells, and is closely related to the biological processes, such as DNA replication, transcription, signal transduction, cell division, stress, microbial aging and pathogenesis. In addition, tRNA plays an essential role in the regulation of gene expression, as effector molecules, no-load tRNA affects the overall gene expression level of cells under some nutritional stress. KptA/Tpt1 is an essential phosphotransferase in the process of pre-tRNA splicing, releasing mature tRNA and participating in ADP-ribose. The objective of this review is concluding the gene structure, the evolution history and the function of KptA/Tpt1 from prokaryote to eukaryote organisms. At the same time, the results of promoter elements analysis were also shown in the present study. Moreover, the problems in the function of KptA/Tpt1 that have not been clarified at the present time are summarised, and some suggestions to solve those problems are given. This review presents no only a summary of clear function of KptA/Tpt1 in the process of tRNA splicing and ADP-ribosylation of organisms, but also gives some proposals to clarify unclear problems of it in the future.
Topics: NAD; Phosphotransferases (Alcohol Group Acceptor); RNA, Transfer; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins
PubMed: 32438974
DOI: 10.1071/FP19159 -
Genes & Genomics Dec 2022Plant growth and development are complex processes modulated by numerous genes, transcription factors, hormones, and peptides. Several reports implicate the...
BACKGROUND
Plant growth and development are complex processes modulated by numerous genes, transcription factors, hormones, and peptides. Several reports implicate the membrane-localized Catharanthus roseus receptor-like kinase1 (CrRLK1L) protein, FERONIA (FER), involved in plant development. However, protein targets of FER remain poorly characterized.
OBJECTIVE
FER recombinant proteins were analyzed, and FER-interacting proteins were identified, to better understand the function of the Arabidopsis thaliana FER (AtFER) gene in plant development.
METHODS
AtFER-interacting proteins were identified through Yeast-Two Hybrid (Y2H) and validated by bimolecular fluorescence complementation (BiFC). Autophosphorylation activity was evaluated in AtFER site-directed and deletion mutants.
RESULTS
AtFER cytoplasmic kinase domain (Flag-FER-CD) is autophosphorylated at the Thr residue (s), with T559 and T664 as important sites for AtFER kinase activity. In addition, the carboxy terminal region is essential for AtFER kinase activity. Y2H identified an Armadillo (ARM)-repeat protein (At4g16490) with tandem copies of a degenerate protein sequence motif, a U-BOX 9 (PUB9, At3g07360), IQ-DOMAIN 7 (IQD7, At1g17480), and heteroglycan glucosidase 1 (HGL1, At3g23640) as AtFER-interacting proteins. BiFC confirmed the in vivo interactions between these four proteins and AtFER in tobacco (Nicotiana benthamiana) leaf transient expression assays. The RAPID ALKALINIZATION FACTOR1 (RALF1) peptide, which is a FER ligand, induced the expression of genes encoding the four AtFER-interacting proteins.
CONCLUSION
The AtFER-interacting proteins identified in this study are likely involved in FER-mediated intracellular signaling pathways that are essential in plant growth and development, and possibly plant immunity.
Topics: Arabidopsis; Arabidopsis Proteins; Peptide Hormones; Phosphotransferases; Phosphorylation
PubMed: 36053485
DOI: 10.1007/s13258-022-01292-3 -
FEBS Letters Jan 2022Cancer cells are challenged by a myriad of microenvironmental stresses, and it is their ability to efficiently adapt to the constantly changing nutrient, energy,... (Review)
Review
Cancer cells are challenged by a myriad of microenvironmental stresses, and it is their ability to efficiently adapt to the constantly changing nutrient, energy, oxidative, and/or immune landscape that allows them to survive and proliferate. Such adaptations, however, result in distinct vulnerabilities that are attractive therapeutic targets. Phosphatidylinositol 5-phosphate 4-kinases (PI5P4Ks) are a family of druggable stress-regulated phosphoinositide kinases that become conditionally essential as a metabolic adaptation, paving the way to targeting cancer cell dependencies. Further, PI5P4Ks have a synthetic lethal interaction with the tumor suppressor p53, the loss of which is one of the most prevalent genetic drivers of malignant transformation. PI5P4K's emergence as a crucial axis in the expanding landscape of phosphoinositide signaling in cancer has already stimulated the development of specific inhibitors. Thus, a better understanding of the biology of the PI5P4Ks will allow for targeted and effective therapeutic interventions. Here, we attempt to summarize the mounting roles of the PI5P4Ks in cancer, including evidence that targeting them is a therapeutic vulnerability and promising next-in-line treatment for multiple cancer subtypes.
Topics: Phosphotransferases (Alcohol Group Acceptor)
PubMed: 34822164
DOI: 10.1002/1873-3468.14237 -
Current Opinion in Chemical Biology Feb 2020Dynamical features of cell signaling are the essence of living organisms. To understand animal development, it is fundamental to investigate signaling dynamics in vivo.... (Review)
Review
Dynamical features of cell signaling are the essence of living organisms. To understand animal development, it is fundamental to investigate signaling dynamics in vivo. Robust reporters are required to visualize spatial and temporal dynamics of enzyme activities and protein-protein interactions involved in signaling pathways. In this review, we summarize recent development in the design of new classes of fluorescent reporters for imaging dynamic activities of proteases, kinases, and protein-protein interactions. These reporters operate on new physical and/or chemical principles; achieve large dynamic range, high brightness, and fast kinetics; and reveal spatiotemporal dynamics of signaling that is correlated with developmental events such as embryonic morphogenesis in live animals including Drosophila and zebrafish. Therefore, many of these reporters are great tools for biological discovery and mechanistic understanding of animal development and disease progression.
Topics: Animals; Fluorescent Dyes; Humans; Image Processing, Computer-Assisted; Optical Imaging; Peptide Hydrolases; Phosphotransferases; Protein Interaction Maps; Signal Transduction
PubMed: 31678813
DOI: 10.1016/j.cbpa.2019.09.004 -
World Journal of Microbiology &... Jul 2020The phosphoenolpyruvate-dependent glucose phosphotransferase system (PTS) is the major uptake system responsible for transporting glucose, and is involved in glucose... (Review)
Review
The phosphoenolpyruvate-dependent glucose phosphotransferase system (PTS) is the major uptake system responsible for transporting glucose, and is involved in glucose translocation and phosphorylation in Corynebacterium glutamicum. For the longest time, the PTS was considered as the only uptake system for glucose. However, some PTS-independent glucose uptake systems (non-PTS) were discovered in recent years, such as the coupling system of inositol permeases and glucokinases (IPGS) and the coupling system of β-glucoside-PTS permease and glucokinases (GPGS). The products (e.g. lysine, phenylalanine and leucine) will be increased because of the increasing intracellular level of phosphoenolpyruvate (PEP), while some by-products (e.g. lactic acid, alanine and acetic acid) will be reduced when this system become the main uptake pathway for glucose. In this review, we survey the uptake systems for glucose in C. glutamicum and their composition. Furthermore, we summarize the latest research of the regulatory mechanisms among these glucose uptake systems. Detailed strategies to manipulate glucose uptake system are addressed based on this knowledge.
Topics: Bacterial Proteins; Biological Transport; Carbohydrate Metabolism; Corynebacterium glutamicum; Glucose; Glucosides; Membrane Proteins; Membrane Transport Proteins; Mutagenesis, Site-Directed; Phosphoenolpyruvate Sugar Phosphotransferase System; Protein Kinases
PubMed: 32712859
DOI: 10.1007/s11274-020-02898-z