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Histology and Histopathology May 2018Sphingosine kinase functions to phosphorylate sphingosine to sphingosine 1-phosphate (S1P) to keep balance in the metabolites of sphingolipids. There are two isoforms of... (Review)
Review
Sphingosine kinase functions to phosphorylate sphingosine to sphingosine 1-phosphate (S1P) to keep balance in the metabolites of sphingolipids. There are two isoforms of sphingosine kinase, sphingosine kinase 1 (SphK1) and sphingosine kinase 2 (SphK2). Although SphK1 and SphK2 share high sequence similarity, SphK2 has distinct distribution, regulation and function. SphK2 is involved in the pathological processes of varieties of diseases including cancer, neurodegenerative disorders, stroke, cardiovascular diseases and inflammation. SphK2 may promote the proliferation of cancer cells and the progression of inflammation. The SphK2/S1P pathway is also involved in the pathogenesis of neurodegenerative disorders and stroke. S1P produced by SphK2 in the nucleus binds to HDACs, which then inhibits histone acetylation and regulates memory. The SphK2 pathway mediates platelet aggregation, thrombosis, cardioprotection and helps to ameliorate hepatic steatosis. This review focuses on the recent advances in research on SphK2 regulation and its potential roles in diseases, highlighting SphK2 may be a novel therapeutic strategy for diseases.
Topics: Animals; Gene Expression Regulation, Enzymologic; Humans; Lysophospholipids; Phosphotransferases (Alcohol Group Acceptor); Sphingosine
PubMed: 29057430
DOI: 10.14670/HH-11-939 -
Trends in Plant Science Jun 2016To develop successfully in an ever-changing environment, it is essential for plants to monitor and control their growth. Therefore, cell expansion is carefully regulated... (Review)
Review
To develop successfully in an ever-changing environment, it is essential for plants to monitor and control their growth. Therefore, cell expansion is carefully regulated to establish correct cell shape and size. In this review, we explore the role of the Catharanthus roseus receptor-like kinase (CrRLK1L) subfamily as regulators of cell expansion. Recently, the downstream signalling events of individual CrRLK1L pathways were discovered, implicating known modulators of cell expansion, such as reactive oxygen species (ROS) production, Ca(2+) dynamics, and exocytosis of cell wall material. Based on these intriguing new insights, we propose a model for a common pathway of CrRLK1L signalling that enables spatial and temporal control of cell wall extensibility throughout the plant.
Topics: Calcium Signaling; Catharanthus; Cell Enlargement; Cell Wall; Models, Biological; Phosphotransferases; Plant Leaves; Plant Proteins; Plant Roots; Reactive Oxygen Species; Reproduction; Signal Transduction
PubMed: 26778775
DOI: 10.1016/j.tplants.2015.12.004 -
Gene May 2023Polypeptides play irreplaceable roles in cell-cell communication by binding to receptor-like kinases. Various types of peptide-receptor-like kinase-mediated signaling... (Review)
Review
Polypeptides play irreplaceable roles in cell-cell communication by binding to receptor-like kinases. Various types of peptide-receptor-like kinase-mediated signaling have been identified in anther development and male-female interactions in flowering plants. Here, we provide a comprehensive summary of the biological functions and signaling pathways of peptides and receptors involved in anther development, self-incompatibility, pollen tube growth and pollen tube guidance.
Topics: Reproduction; Signal Transduction; Cell Communication; Phosphotransferases; Pollen; Peptides; Flowers
PubMed: 36870426
DOI: 10.1016/j.gene.2023.147328 -
Nucleic Acids Research Jan 2021Mutations in kinases are abundant and critical to study signaling pathways and regulatory roles in human disease, especially in cancer. Somatic mutations in kinase genes...
Mutations in kinases are abundant and critical to study signaling pathways and regulatory roles in human disease, especially in cancer. Somatic mutations in kinase genes can affect drug treatment, both sensitivity and resistance, to clinically used kinase inhibitors. Here, we present a newly constructed database, KinaseMD (kinase mutations and drug response), to structurally and functionally annotate kinase mutations. KinaseMD integrates 679 374 somatic mutations, 251 522 network-rewiring events, and 390 460 drug response records curated from various sources for 547 kinases. We uniquely annotate the mutations and kinase inhibitor response in four types of protein substructures (gatekeeper, A-loop, G-loop and αC-helix) that are linked to kinase inhibitor resistance in literature. In addition, we annotate functional mutations that may rewire kinase regulatory network and report four phosphorylation signals (gain, loss, up-regulation and down-regulation). Overall, KinaseMD provides the most updated information on mutations, unique annotations of drug response especially drug resistance and functional sites of kinases. KinaseMD is accessible at https://bioinfo.uth.edu/kmd/, having functions for searching, browsing and downloading data. To our knowledge, there has been no systematic annotation of these structural mutations linking to kinase inhibitor response. In summary, KinaseMD is a centralized database for kinase mutations and drug response.
Topics: Databases, Genetic; Drug Resistance, Neoplasm; Molecular Sequence Annotation; Mutation; Phosphorylation; Phosphotransferases; Protein Kinase Inhibitors; User-Computer Interface
PubMed: 33137204
DOI: 10.1093/nar/gkaa945 -
Trends in Cell Biology Sep 2014Pseudophosphatases and pseudokinases are increasingly viewed as integral elements of signaling pathways, and there is mounting evidence that they have frequently... (Review)
Review
Pseudophosphatases and pseudokinases are increasingly viewed as integral elements of signaling pathways, and there is mounting evidence that they have frequently retained the ability to interact with cellular 'substrates', and can exert important roles in different diseases. However, these pseudoenzymes have traditionally received scant attention compared to classical kinases and phosphatases. In this review we explore new findings in the emerging pseudokinase and pseudophosphatase fields, and discuss their different modes of action which include exciting new roles as scaffolds, anchors, spatial modulators, traps, and ligand-driven regulators of canonical kinases and phosphatases. Thus, it is now apparent that pseudokinases and pseudophosphatases both support and drive a panoply of signaling networks. Finally, we highlight recent evidence on their involvement in human pathologies, marking them as potential novel drug targets.
Topics: Adenosine Triphosphate; Humans; Neoplasms; Phosphoric Monoester Hydrolases; Phosphotransferases; Signal Transduction
PubMed: 24818526
DOI: 10.1016/j.tcb.2014.03.008 -
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 -
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 -
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 -
Fungal Genetics and Biology : FG & B May 2016The striatin-interacting phosphatases and kinases (STRIPAK) complex is a highly conserved eukaryotic protein complex that was recently described for diverse animal and... (Review)
Review
The striatin-interacting phosphatases and kinases (STRIPAK) complex is a highly conserved eukaryotic protein complex that was recently described for diverse animal and fungal species. Here, we summarize our current knowledge about the composition and function of the STRIPAK complex from the ascomycete Sordaria macrospora, which we discovered by investigating sexually sterile mutants (pro), having a defect in fruiting body development. Mass spectrometry and yeast two-hybrid analysis defined core subunits of the STRIPAK complex, which have structural homologs in animal and other fungal organisms. These subunits (and their mammalian homologs) are PRO11 (striatin), PRO22 (STRIP1/2), SmMOB3 (Mob3), PRO45 (SLMAP), and PP2AA, the structural, and PP2Ac, the catalytic subunits of protein phosphatase 2A (PP2A). Beside fruiting body formation, the STRIPAK complex controls vegetative growth and hyphal fusion in S. macrospora. Although the contribution of single subunits to diverse cellular and developmental processes is not yet fully understood, functional analysis has already shown that mammalian homologs are able to substitute the function of distinct fungal STRIPAK subunits. This underscores the view that fungal model organisms serve as useful tools to get a molecular insight into cellular and developmental processes of eukaryotes in general. Future work will unravel the precise localization of single subunits within the cell and decipher their STRIPAK-related and STRIPAK-independent functions. Finally, evidence is accumulating that there is a crosstalk between STRIPAK and various signaling pathways, suggesting that eukaryotic development is dependent on STRIPAK signaling.
Topics: Animals; Fungal Proteins; Fungi; Humans; Phosphoric Monoester Hydrolases; Phosphotransferases; Signal Transduction; Species Specificity
PubMed: 26439752
DOI: 10.1016/j.fgb.2015.10.001