21,617 results match your criteria kinase cascade

Evolution of the membrane/particulate guanylyl cyclase: from physicochemical sensors to hormone receptors.

Yoshio Takei

Gen Comp Endocrinol 2021 May 3:113797. Epub 2021 May 3.

Laboratory of Physiology, Department of Marine Bioscience, Atmosphere and Ocean Research Institute, The University of Tokyo, Kashiwa, Chiba 277-8564, Japan. Electronic address:

Guanylyl cyclase (GC) is an enzyme that produces 3',5'-cyclic guanosine monophosphate (cGMP), one of the two canonical cyclic nucleotides used as a second messenger for intracellular signal transduction. The GCs are classified into two groups, particulate/membrane GCs (pGC) and soluble/cytosolic GCs (sGC). In relation to the endocrine system, pGCs include hormone receptors for natriuretic peptides (GC-A and GC-B) and guanylin peptides (GC-C), while sGC is a receptor for nitric oxide and carbon monoxide. Read More

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A signalling cascade for Ral.

Small GTPases 2021 May 6:1-8. Epub 2021 May 6.

Texas A&M University, Houston, TX, USA.

Ras is the most mutated oncoprotein in cancer. Among the three oncogenic effectors of Ras - Raf, PI3 Kinase and RalGEF>Ral - signalling through RalGEF>Ral (Ras-like) is by far the least well understood. A variety of signals and binding partners have been defined for Ral, yet we know little of how Ral functions . Read More

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Corrigendum to: Mitogen-activated protein kinase kinase 5 (MKK5)-mediated signaling cascade regulates expression of iron superoxide dismutase gene in Arabidopsis under salinity stress.

J Exp Bot 2021 May 6. Epub 2021 May 6.

School of Life Sciences, State Key Laboratory of Agrobiotechnology, and Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China.

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The Scaffold Proteins Paxillin B and α-Actinin Regulate Septation in Aspergillus nidulans via Control of Actin Ring Contraction.

Genetics 2020 Jun;215(2):449-461

Jiangsu Key Laboratory for Microbes and Functional Genomics, College of Life Sciences, Nanjing Normal University, 210023, China.

Cytokinesis, as the final step of cell division, plays an important role in fungal growth and proliferation. In the filamentous fungus Aspergillus nidulans, defective cytokinesis is able to induce abnormal multinuclear or nonnucleated cells and then result in reduced hyphal growth and abolished sporulation. Previous studies have reported that a conserved contractile actin ring (CAR) protein complex and the septation initiation network (SIN) signaling kinase cascade are required for cytokinesis and septation; however, little is known about the role(s) of scaffold proteins involved in these two important cellular processes. Read More

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Photobiomodulation therapy promotes the ATP-binding cassette transporter A1-dependent cholesterol efflux in macrophage to ameliorate atherosclerosis.

J Cell Mol Med 2021 May 5. Epub 2021 May 5.

MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, China.

Atherosclerosis is a chronic inflammatory disease related to a massive accumulation of cholesterol in the artery wall. Photobiomodulation therapy (PBMT) has been reported to possess cardioprotective effects but has no consensus on the underlying mechanisms. Here, we aimed to investigate whether PBMT could ameliorate atherosclerosis and explore the potential molecular mechanisms. Read More

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Hippo signaling pathway in companion animal diseases, an under investigated signaling cascade.

Vet Q 2021 May 4:1-14. Epub 2021 May 4.

Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 104, 3584 CM, Utrecht, the Netherlands.

The Hippo pathway is a highly conserved kinase cascade in mammals with the proteins YAP and TAZ as its most important downstream effectors that shuttle between cytoplasma and nucleus. It has a crucial role in processes such as embryogenesis, organ size control, homeostasis and tissue regeneration, where mechanosensing and/or cell-cell interactions are involved. As the pathway is associated with many essential functions in the body, its dysregulation is related to many diseases. Read More

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Bioinformatic analysis and validation of microRNA-508-3p as a protective predictor by targeting NR4A3/MEK axis in pulmonary arterial hypertension.

J Cell Mol Med 2021 May 4. Epub 2021 May 4.

Department of Anesthesiology, Qilu Hospital of Shandong University, Jinan, China.

Pulmonary arterial hypertension (PAH) featured a debilitating progressive disorder. Here, we intend to determine diagnosis-valuable biomarkers for PAH and decode the fundamental mechanisms of the biological function of these markers. Two mRNA microarray profiles (GSE70456 and GSE117261) and two microRNA microarray profiles (GSE55427 and GSE67597) were mined from the Gene Expression Omnibus platform. Read More

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Calculating Transfer Entropy from Variance-Covariance Matrices Provides Insight into Allosteric Communication in ERK2.

J Chem Theory Comput 2021 Apr 30. Epub 2021 Apr 30.

Department of Chemistry, University of Mary, Bismarck, North Dakota 58504, United States.

We develop an approach by which reliable estimates of the transfer entropy can be obtained from the variance-covariance matrix of atomic fluctuations, which converges quickly and retains sensitivity to the full chemical profile of the biomolecular system. We validate our method on ERK2, a well-studied kinase involved in the MAPK signaling cascade for which considerable computational, experimental, and mutation data are available. We present the results of transfer entropy analysis on data obtained from molecular dynamics simulations of wild-type active and inactive ERK2, along with mutants Q103A, I84A, L73P, and G83A. Read More

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Estrogen Receptor Functions and Pathways at the Vascular Immune Interface.

Int J Mol Sci 2021 Apr 20;22(8). Epub 2021 Apr 20.

Department of Medicine, University of Padova, 35128 Padova, Italy.

Estrogen receptor (ER) activity mediates multiple physiological processes in the cardiovascular system. ERα and ERβ are ligand-activated transcription factors of the nuclear hormone receptor superfamily, while the G protein-coupled estrogen receptor (GPER) mediates estrogenic signals by modulating non-nuclear second messengers, including activation of the MAP kinase signaling cascade. Membrane localizations of ERs are generally associated with rapid, non-genomic effects while nuclear localizations are associated with nuclear activities/transcriptional modulation of target genes. Read More

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A Multi-Enzyme Cascade Reaction for the Production of 2'3'-cGAMP.

Biomolecules 2021 Apr 16;11(4). Epub 2021 Apr 16.

Chair for Bioprocess Engineering, Department of Biochemical and Chemical Engineering, TU Dortmund University, D-44227 Dortmund, Germany.

Multi-enzyme cascade reactions for the synthesis of complex products have gained importance in recent decades. Their advantages compared to single biotransformations include the possibility to synthesize complex molecules without purification of reaction intermediates, easier handling of unstable intermediates, and dealing with unfavorable thermodynamics by coupled equilibria. In this study, a four-enzyme cascade consisting of ADK, PPK2, and PPK2 for ATP synthesis from adenosine coupled to the cyclic GMP-AMP synthase (cGAS) catalyzing cyclic GMP-AMP (2'3'-cGAMP) formation was successfully developed. Read More

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Regulation of Cardiac PKA Signaling by cAMP and Oxidants.

Antioxidants (Basel) 2021 Apr 24;10(5). Epub 2021 Apr 24.

Institute of Experimental Pharmacology and Toxicology, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.

Pathologies, such as cancer, inflammatory and cardiac diseases are commonly associated with long-term increased production and release of reactive oxygen species referred to as oxidative stress. Thereby, protein oxidation conveys protein dysfunction and contributes to disease progression. Importantly, trials to scavenge oxidants by systemic antioxidant therapy failed. Read More

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Mind the Gap: LRRK2 Phenotypes in the Clinic vs. in Patient Cells.

Cells 2021 Apr 22;10(5). Epub 2021 Apr 22.

UMR-S 1172-LilNCog-Lille Neuroscience & Cognition, Université de Lille, Inserm, CHU Lille, F-59000 Lille, France.

Mutations in the Parkinson's disease (PD) protein Leucine Rich Repeat Kinase 2 (LRRK2) have been under study for more than 15 years and our understanding of the cellular phenotypes for the pathogenic mutant forms of LRRK2 has significantly advanced. In parallel to research on LRRK2 mutations in experimental systems, clinical characterization of patients carrying LRRK2 mutations has advanced, as has the analysis of cells that are derived from these patients, including fibroblasts, blood-derived cells, or cells rendered pluripotent. Under the hypothesis that patient clinical phenotypes are a consequence of a cascade of underlying molecular mechanisms gone astray, we currently have a unique opportunity to compare findings from patients and patient-derived cells to ask the question of whether the clinical phenotype of LRRK2 Parkinson's disease and cellular phenotypes of LRRK2 patient-derived cells may be mutually informative. Read More

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A Reversible Shift of Driver Dependence from EGFR to Notch1 in Non-Small Cell Lung Cancer as a Cause of Resistance to Tyrosine Kinase Inhibitors.

Cancers (Basel) 2021 Apr 22;13(9). Epub 2021 Apr 22.

Department of Advanced Biomedical Sciences, University "Federico II", 80131 Naples, Italy.

Notch1 plays a key role in epithelial-mesenchymal transition (EMT) and in the maintenance of cancer stem cells. In the present study we tested whether high levels of activated Notch1 in oncogene-driven NSCLC can induce a reversible shift of driver dependence from EGFR to Notch1, and thus causing resistance to EGFR inhibitors. Adherent cells (parental) and tumor spheres (TS) from NSCLC H1975 cells and patient-derived CD133-positive cells were tested for EGFR and Notch1 signaling cascade. Read More

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Ca Microdomains, Calcineurin and the Regulation of Gene Transcription.

Cells 2021 Apr 12;10(4). Epub 2021 Apr 12.

Department of Medical Biochemistry and Molecular Biology, Saarland University Medical Faculty, D-66421 Homburg, Germany.

Ca ions function as second messengers regulating many intracellular events, including neurotransmitter release, exocytosis, muscle contraction, metabolism and gene transcription. Cells of a multicellular organism express a variety of cell-surface receptors and channels that trigger an increase of the intracellular Ca concentration upon stimulation. The elevated Ca concentration is not uniformly distributed within the cytoplasm but is organized in subcellular microdomains with high and low concentrations of Ca at different locations in the cell. Read More

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PINK1: A Bridge between Mitochondria and Parkinson's Disease.

Life (Basel) 2021 Apr 21;11(5). Epub 2021 Apr 21.

Faculdade de Medicina, Instituto de Medicina Molecular-João Lobo Antunes, Universidade de Lisboa, 1649-028 Lisbon, Portugal.

Mitochondria are known as highly dynamic organelles essential for energy production. Intriguingly, in the recent years, mitochondria have revealed the ability to maintain cell homeostasis and ultimately regulate cell fate. This regulation is achieved by evoking mitochondrial quality control pathways that are capable of sensing the overall status of the cellular environment. Read More

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Two VQ Proteins are Substrates of the OsMPKK6-OsMPK4 Cascade in Rice Defense Against Bacterial Blight.

Rice (N Y) 2021 Apr 28;14(1):39. Epub 2021 Apr 28.

National Key Laboratory of Crop Genetic Improvement, National Center of Plant Gene Research (Wuhan), Huazhong Agricultural University, Wuhan, 430070, China.

Background: The plant-specific valine-glutamine (VQ) protein family with the conserved motif FxxxVQxLTG reportedly functions with the mitogen-activated protein kinase (MAPK) in plant immunity. However, the roles of VQ proteins in MAPK-mediated resistance to disease in rice remain largely unknown.

Results: In this study, two rice VQ proteins OsVQ14 and OsVQ32 were newly identified to function as the signaling components of a MAPK cascade, OsMPKK6-OsMPK4, to regulate rice resistance to Xanthomonas oryzae pv. Read More

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Stochastic modulation evidences a transitory EGF-Ras-ERK MAPK activity induced by PRMT5.

Comput Biol Med 2021 Apr 20;133:104339. Epub 2021 Apr 20.

Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain; CIBER of Diabetes and Associated Metabolic Diseases, Barcelona, Spain; Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, University of Barcelona, Barcelona, Spain.

The extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) pathway involves a three-step cascade of kinases that transduce signals and promote processes such as cell growth, development, and apoptosis. An aberrant response of this pathway is related to the proliferation of cell diseases and tumors. By using simulation modeling, we document that the protein arginine methyltransferase 5 (PRMT5) modulates the MAPK pathway and thus avoids an aberrant behavior. Read More

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EPHB2 activates β-catenin to enhance cancer stem cell properties and drive sorafenib resistance in hepatocellular carcinoma.

Cancer Res 2021 Apr 26. Epub 2021 Apr 26.

Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University

The survival benefit derived from sorafenib treatment for patients with hepatocellular carcinoma (HCC) is modest due to acquired resistance. Targeting cancer stem cells (CSC) is a possible way to reverse drug resistance; however, inhibitors that specifically target liver CSCs are limited. In this study, we established two sorafenib-resistant, patient-derived tumor xenografts (PDX) that mimicked development of acquired resistance to sorafenib in HCC patients. Read More

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KIBRA Connects Hippo Signaling and Cancer.

Exp Cell Res 2021 Apr 23:112613. Epub 2021 Apr 23.

Department of Human Genetics, Faculty of Biomedical Sciences, Technology & Research, Sri Ramachandra Institute of Higher Education, Chennai, 600116, Tamil Nadu, India. Electronic address:

The Hippo signaling pathway is a tumor suppressor pathway that plays an important role in tissue homeostasis and organ size control. KIBRA is one of the many upstream regulators of the Hippo pathway. It functions as a tumor suppressor by positively regulating the core Hippo kinase cascade. Read More

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Subunit P60 of phosphatidylinositol 3-kinase promotes cell proliferation or apoptosis depending on its phosphorylation status.

PLoS Genet 2021 Apr 26;17(4):e1009514. Epub 2021 Apr 26.

Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Qingdao, China.

The regulatory subunits (P60 in insects, P85 in mammals) determine the activation of the catalytic subunits P110 in phosphatidylinositol 3-kinases (PI3Ks) in the insulin pathway for cell proliferation and body growth. However, the regulatory subunits also promote apoptosis via an unclear regulatory mechanism. Using Helicoverpa armigera, an agricultural pest, we showed that H. Read More

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AMPKα2 activation by an energy-independent signal ensures chromosomal stability during mitosis.

iScience 2021 Apr 26;24(4):102363. Epub 2021 Mar 26.

MOE Key Laboratory for Membraneless Organelles and Cellular Dynamics, University of Science & Technology of China School of Life Sciences, Hefei 230027, China.

AMP-activated protein kinase (AMPK) senses energy status and impacts energy-consuming events by initiating metabolism regulatory signals in cells. Accumulating evidences suggest a role of AMPK in mitosis regulation, but the mechanism of mitotic AMPK activation and function remains elusive. Here we report that AMPKα2, but not AMPKα1, is sequentially phosphorylated and activated by CDK1 and PLK1, which enables AMPKα2 to accurately guide chromosome segregation in mitosis. Read More

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Mini review: The FDA-approved prescription drugs that target the MAPK signaling pathway in women with breast cancer.

Breast Dis 2021 Mar 8. Epub 2021 Mar 8.

Fertility, Infertility and Perinatology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Breast cancer (BC) is the most common cancer and the prevalent type of malignancy among women. Multiple risk factors, including genetic changes, biological age, dense breast tissue, and obesity are associated with BC. The mitogen-activated protein kinases (MAPK) signaling pathway has a pivotal role in regulating biological functions such as cell proliferation, differentiation, apoptosis, and survival. Read More

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Reconstitution of cargo-induced LC3 lipidation in mammalian selective autophagy.

Sci Adv 2021 Apr 23;7(17). Epub 2021 Apr 23.

Department of Molecular and Cell Biology and California Institute for Quantitative Biosciences, University of California, Berkeley, Berkeley, CA 94720, USA.

Selective autophagy of damaged mitochondria, protein aggregates, and other cargoes is essential for health. Cargo initiates phagophore biogenesis, which entails the conjugation of LC3 to phosphatidylethanolamine. Current models suggest that clustered ubiquitin chains on a cargo trigger a cascade from autophagic cargo receptors through the core complexes ULK1 and class III phosphatidylinositol 3-kinase complex I, WIPI2, and the ATG7, ATG3, and ATG12ATG5-ATG16L1 machinery of LC3 lipidation. Read More

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A phylogenetic study of the members of the MAPK and MEK families across Viridiplantae.

PLoS One 2021 23;16(4):e0250584. Epub 2021 Apr 23.

Departamento de Biología Molecular de Plantas, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, México.

Protein phosphorylation is regulated by the activity of enzymes generically known as kinases. One of those kinases is Mitogen-Activated Protein Kinases (MAPK), which operate through a phosphorylation cascade conformed by members from three related protein kinase families namely MAPK kinase kinase (MEKK), MAPK kinase (MEK), and MAPK; these three acts hierarchically. Establishing the evolution of these proteins in the plant kingdom is an interesting but complicated task because the current MAPK, MAPKK, and MAPKKK subfamilies arose from duplications and subsequent sub-functionalization during the early stage of the emergence of Viridiplantae. Read More

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Smoothened transduces Hedgehog signals via activity-dependent sequestration of PKA catalytic subunits.

PLoS Biol 2021 Apr 22;19(4):e3001191. Epub 2021 Apr 22.

Department of Oncological Sciences, Department of Biochemistry, Department of Bioengineering, University of Utah School of Medicine, Salt Lake City, Utah, United States of America.

The Hedgehog (Hh) pathway is essential for organ development, homeostasis, and regeneration. Dysfunction of this cascade drives several cancers. To control expression of pathway target genes, the G protein-coupled receptor (GPCR) Smoothened (SMO) activates glioma-associated (GLI) transcription factors via an unknown mechanism. Read More

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Integrin αVβ1 Regulates Procollagen I Production through a Non-canonical Transforming Growth Factor β Signaling Pathway in Human Hepatic Stellate Cells.

Biochem J 2021 Apr 20. Epub 2021 Apr 20.

Bristol-Myers Squibb Company, Princeton, New Jersey, United States.

Hepatic stellate cells (HSCs) are thought to play key roles in the development of liver fibrosis.  Extensive evidence has established the concept that αV integrins are involved in the activation of latent transforming growth factor β (TGF-β), a master regulator of the fibrotic signaling cascade.  Based on mRNA and protein expression profiling data, we found that αVβ1 integrin is the most abundant member of the αV integrin family in either quiescent or TGF-β1-activated primary human HSCs. Read More

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Hippo-Independent Regulation of Yki/Yap/Taz: A Non-canonical View.

Front Cell Dev Biol 2021 1;9:658481. Epub 2021 Apr 1.

Department of Molecular Biology, UT Southwestern Medical Center, Dallas, TX, United States.

Initially identified in , the Hippo signaling pathway has emerged as an evolutionarily conserved tumor suppressor pathway that controls tissue growth and organ size by simultaneously inhibiting cell proliferation and promoting cell death. Deregulation of Hippo pathway activity has been implicated in a wide range of human cancers. The core Hippo pathway consists of a kinase cascade: an upstream kinase Hippo (Hpo)/MST1/2 phosphorylates and activates a downstream kinase Warts (Wts)/Lats1/2, leading to phosphorylation and inactivation of a transcriptional coactivator Yki/YAP/Taz. Read More

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Role of NFAT in Chronic Lymphocytic Leukemia and Other B-Cell Malignancies.

Front Oncol 2021 1;11:651057. Epub 2021 Apr 1.

Division of Experimental Oncology, San Raffaele Hospital IRCCS, Milano, Italy.

In recent years significant progress has been made in the clinical management of chronic lymphocytic leukemia (CLL) as well as other B-cell malignancies; targeting proximal B-cell receptor signaling molecules such as Bruton Tyrosine Kinase (BTK) and Phosphoinositide 3-kinase (PI3Kδ) has emerged as a successful treatment strategy. Unfortunately, a proportion of patients are still not cured with available therapeutic options, thus efforts devoted to studying and identifying new potential druggable targets are warranted. B-cell receptor stimulation triggers a complex cascade of signaling events that eventually drives the activation of downstream transcription factors including Nuclear Factor of Activated T cells (NFAT). Read More

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PP2A and E3 ubiquitin ligase deficiencies: Seminal biological drivers in endometrial cancer.

Gynecol Oncol 2021 Apr 15. Epub 2021 Apr 15.

Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, MN, United States of America. Electronic address:

Objective: PI3K-AKT pathway mutations initiate a kinase cascade that characterizes endometrial cancer (EC). As kinases seldom cause oncogenic transformation without dysregulation of antagonistic phosphatases, pivotal interactions governing this pathway were explored and correlated with clinical outcomes.

Methods: After exclusion of patients with POLE mutations from The Cancer Genome Atlas EC cohort with endometrioid or serous EC, the study population was 209 patients with DNA sequencing, quantitative gene-specific RNA expression, copy number variation (CNV), and surveillance data available. Read More

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HEAT SHOCK PROTEIN 90 proteins and YODA regulate main body axis formation during early embryogenesis.

Plant Physiol 2021 Apr 15. Epub 2021 Apr 15.

Centre of the Region Haná for Biotechnological and Agricultural Research, Faculty of Science, Palacký University Olomouc, Šlechtitelů 27, 783 71 Olomouc, Czech Republic.

The YODA kinase (YDA) pathway is intimately associated with the control of Arabidopsis (Arabidopsis thaliana) embryo development, but little is known regarding its regulators. Using genetic analysis, HEAT SHOCK PROTEIN 90 (HSP90) proteins emerge as potent regulators of YDA in the process of embryo development and patterning. This study is focused on the characterization and quantification of early embryonal traits of single and double hsp90 and yda mutants. Read More

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