scholarly journals Saccharomyces cerevisiae Env7 is a novel serine/threonine kinase 16 (STK16)‐related protein kinase and negatively regulates organelle fusion at the lysosomal vacuole

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Editte Gharakhanian ◽  
Surya Manandhar ◽  
Florante Ricarte ◽  
Stephanie Cocca
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Protein Kinase ◽  
Related Protein ◽  
Serine Threonine Kinase ◽  
Threonine Kinase

A visible light-controllable Rho kinase inhibitor based on a photochromic phenylazothiazole

2021 ◽  
Author(s):  
Kazuya Matsuo ◽  
Sampreeth Thayyil ◽  
Mitsuyasu Kawaguchi ◽  
Hidehiko Nakagawa ◽  
Nobuyuki Tamaoki
Keyword(s):  
Protein Kinase ◽  
Visible Light ◽  
Kinase Inhibitor ◽  
Coiled Coil ◽  
Rho Kinase ◽  
Rock Inhibitor ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Rho Kinase Inhibitor

Rho-associated coiled-coil-containing protein kinase (ROCK) is a serine-threonine kinase, whose inhibitors are useful for the regulation of actomyosin system. Here, we developed a photoswitchable ROCK inhibitor based on a phenylazothiazole...

scholarly journals Chlorpyrifos Suppresses Neutrophil Extracellular Traps in Carp by Promoting Necroptosis and Inhibiting Respiratory Burst Caused by the PKC/MAPK Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Qiaojian Zhang ◽  
Shengchen Wang ◽  
Shufang Zheng ◽  
Ziwei Zhang ◽  
Shiwen Xu
Keyword(s):  
Protein Kinase ◽  
Respiratory Burst ◽  
Mapk Pathway ◽  
Organophosphorus Pesticide ◽  
Neutrophil Extracellular Traps ◽  
Mitogen Activated Protein Kinase ◽  
Serine Threonine Kinase ◽  
Expression Levels ◽  
Threonine Kinase ◽  
Extracellular Traps

Neutrophil extracellular traps (NETs) are reticular structures formed by myeloperoxidase (MPO), histones, and neutrophil elastase (NE) that are released from neutrophils in response to pathogenic stimuli. Chlorpyrifos (CPF) is wildly used as an organophosphorus pesticide that causes a range of toxicological and environmental problems. Exposure to CPF can increase the production of neutrophils in carps, and this increase can be considered a biomarker of water pollution. To explore a relationship between NETs and CPF and its mechanism of influence, we treated neutrophils from the blood of carp with 1 μg/mL phorbol 12-myristate 13-acetate (PMA), 0.325 mg/L CPF, or 20 μM necrostatin-1 (Nec-1). The production of MPO and NETs was reduced in the CPF+PMA group compared with that in the PMA group. CPF can cause an increase in reactive oxygen species (ROS), while inhibiting respiratory burst caused by PMA stimulation. We found that the expression levels of protein-coupled receptor 84 (gpr84), dystroglycan (DAG), proto-oncogene serine/threonine kinase (RAF), protein kinase C (PKC), and mitogen-activated protein kinase 3 (MAPK3) in the CPF+PMA group were lower than those in the PMA group, indicating that the PKC-MAPK pathway was suppressed. The expression levels of cylindromatosis (CYLD), mixed lineage kinase domain-like pseudokinase (MLKL), receptor-interacting serine-threonine kinase 1 (RIP1), and receptor-interacting serine-threonine kinase 3 (RIP3) were increased, and the expression levels of caspase 8 were reduced by CPF, indicating that CPF may cause necroptosis. The addition of Nec-1 restored the number of NETs in the CPF+PMA group. The results indicate that CPF reduced the production of NETs by inhibiting respiratory burst and increasing necroptosis. The results contribute to the understanding of the immunotoxicological mechanism of CPF and provide a reference for comparative medical studies.

scholarly journals Membrane localization of the kinase which phosphorylates p34cdc2 on threonine 14.

1994 ◽  
Vol 5 (3) ◽  
pp. 273-282 ◽  
Author(s):  
S Kornbluth ◽  
B Sebastian ◽  
T Hunter ◽  
J Newport
Keyword(s):  
Cell Cycle ◽  
Protein Kinase ◽  
Schizosaccharomyces Pombe ◽  
Protein Kinases ◽  
Membrane Fraction ◽  
Kinase Activity ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Dual Specificity ◽  
Detergent Extraction

The key regulator of entry into mitosis is the serine/threonine kinase p34cdc2. This kinase is regulated both by association with cyclins and by phosphorylation at several sites. Phosphorylation at Tyr 15 and Thr 14 are believed to inhibit the kinase activity of cdc2. In Schizosaccharomyces pombe, the wee1 (and possibly mik1) protein kinase catalyzes phosphorylation of Tyr 15. It is not clear whether these or other, as yet unidentified, protein kinases phosphorylate Thr 14. In this report we show, using extracts of Xenopus eggs, that the Thr 14-directed kinase is tightly membrane associated. Specifically, we have shown that a purified membrane fraction, in the absence of cytoplasm, can promote phosphorylation of cdc2 on both Thr 14 and Tyr 15. In contrast, the cytoplasm can phosphorylate cdc2 only on Tyr 15, suggesting the existence of at least two distinctly localized subpopulations of cdc2 Tyr 15-directed kinases. The membrane-associated Tyr 15 and Thr 14 kinase activities behaved similarly during salt or detergent extraction and were similarly regulated during the cell cycle and by the checkpoint machinery that delays mitosis while DNA is being replicated. This suggests the possibility that a dual-specificity membrane-associated protein kinase may catalyze phosphorylation of both Tyr 15 and Thr 14.

PRKD2 Serine-Threonine Kinase, a Downstream Effector Of GABP, Plays Essential Roles For The Maintenance Of HSCs

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2430-2430
Author(s):  
Zhong-Fa Yang ◽  
Wang Junling ◽  
Alan G. Rosmarin
Keyword(s):  
Bone Marrow ◽  
Transcription Factor ◽  
Protein Kinase ◽  
Bone Marrow Cells ◽  
Specific Cell ◽  
Wild Type ◽  
Serine Threonine Kinase ◽  
Hematopoietic Stem ◽  
Threonine Kinase ◽  
Marrow Cells

Abstract Hematopoietic stem cells (HSCs) are the source of all blood lineages, and HSCs must balance quiescence, self-renewal, and differentiation to meet lifelong needs for blood cell development. GABP is an ets-related transcription factor that controls critical genes in myeloid and lymphoid development, and has been implicated in control of HSC growth. GABP is an obligate multimeric transcription factor that includes the DNA-binding ets component, GABPa, along with various GABPb partner proteins. We conditionally deleted Gabpa in mouse bone marrow and found that Gabpa cells have a profound growth disadvantage due to cell cycle arrest in HSCs. We identified Protein Kinase D2 (PRKD2) as a candidate effector of GABP. PRKD2 is a diacyl glycerol- and Protein Kinase C-activated serine-threonine kinase, because deletion of Gabpa markedly reduced PRKD2 expression in normal HSCs and progenitor cells. In a Prkd2ki/ki mouse model, in which two functionally essential phosphorylation serines were inactivated genetically, their bone marrow long term HSCs reduced dramatically and the short term HSCs increased accordingly. Mice transplanted with a 1:1 mixture of Prkd2ki/ki and wild type bone marrow cells demonstrated the decreased proportion of the Prkd2ki/ki bone marrow cells with the corresponding increase of the wild type cells. Although ectopic expression of the human Chronic Myeloid Leukemia (CML) fusion oncogene BCR-ABL in wild type bone marrow cells induced rapid CML development, expression of BCR-ABL in Prkd2ki/ki bone marrow cells failed to develop CML in transplanted recipient mice. Analysis of the peripheral blood, bone marrow and spleen of these mice revealed that the BCR-ABL+, Prkd2ki/ki cells did not express myeloid or lymphoid specific cell surface antigens CD11b, Gr1, B220, or CD3e. They demonstrated an immature blast-like microscopic morphology, and recipient mice transplanted with these cells died before the onset of CML development. We conclude that the phosphorylation activated Prkd2 is required for the maintenance of HSC pool and the development of mature hematopoietic lineages from HSCs. These findings suggest that PRKD2 kinase mediate key downstream events of both PKC and transcription factor GABP, and that PRKD2 may serve as a novel therapeutic target in leukemia. Disclosures: No relevant conflicts of interest to declare.

Development of a Transcreener™ Kinase Assay for Protein Kinase A and Demonstration of Concordance of Data with a Filter-Binding Assay Format

2007 ◽  
Vol 12 (4) ◽  
pp. 578-584 ◽  
Author(s):  
Karen L. Huss ◽  
Pauline E. Blonigen ◽  
Robert M. Campbell
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Fluorescence Polarization ◽  
Binding Assay ◽  
Kinase Assay ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Alexa Fluor ◽  
Small Molecule Library ◽  
Kinase A

A Transcreener™ kinase fluorescence polarization (FP) assay has been developed for the serine/threonine kinase protein kinase A (PKA). The PKA Transcreener™ kinase assay is an homogenous, competitive antibody-based FP assay that uses Far Red Alexa Fluor 633-labeled adenosine 5′ disphosphate (ADP) tracer and mouse monoclonal anti-ADP antibody. The Transcreener™ PKA assay was validated with both known PKA inhibitors and library compounds. The Transcreener™ PKA assay is resistant to low-wavelength (or common) fluorescent interference from small-molecule library compounds and generates IC50 results comparable with current radioactive filter-binding assay. ( Journal of Biomolecular Screening 2007:578-584)

scholarly journals The Cell Cycle Checkpoint System MAST(L)-ENSA/ARPP19-PP2A is Targeted by cAMP/PKA and cGMP/PKG in Anucleate Human Platelets

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 472 ◽  
Author(s):  
Elena J. Kumm ◽  
Oliver Pagel ◽  
Stepan Gambaryan ◽  
Ulrich Walter ◽  
René P. Zahedi ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Protein Kinase ◽  
Map Kinases ◽  
Human Platelets ◽  
Cell Cycle Checkpoint ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Proteomic Data ◽  
Cycle Checkpoint ◽  
Phosphatase 2A

The cell cycle is controlled by microtubule-associated serine/threonine kinase-like (MASTL), which phosphorylates the cAMP-regulated phosphoproteins 19 (ARPP19) at S62 and 19e/α-endosulfine (ENSA) at S67and converts them into protein phosphatase 2A (PP2A) inhibitors. Based on initial proteomic data, we hypothesized that the MASTL-ENSA/ARPP19-PP2A pathway, unknown until now in platelets, is regulated and functional in these anucleate cells. We detected ENSA, ARPP19 and various PP2A subunits (including seven different PP2A B-subunits) in proteomic studies of human platelets. ENSA-S109/ARPP19–S104 were efficiently phosphorylated in platelets treated with cAMP- (iloprost) and cGMP-elevating (NO donors/riociguat) agents. ENSA-S67/ARPP19-S62 phosphorylations increased following PP2A inhibition by okadaic acid (OA) in intact and lysed platelets indicating the presence of MASTL or a related protein kinase in human platelets. These data were validated with recombinant ENSA/ARPP19 and phospho-mutants using recombinant MASTL, protein kinase A and G. Both ARPP19 phosphorylation sites S62/S104 were dephosphorylated by platelet PP2A, but only S62-phosphorylated ARPP19 acted as PP2A inhibitor. Low-dose OA treatment of platelets caused PP2A inhibition, diminished thrombin-stimulated platelet aggregation and increased phosphorylation of distinct sites of VASP, Akt, p38 and ERK1/2 MAP kinases. In summary, our data establish the entire MASTL(like)–ENSA/ARPP19–PP2A pathway in human platelets and important interactions with the PKA, MAPK and PI3K/Akt systems.

scholarly journals Elucidating TOR Signaling and Rapamycin Action: Lessons from Saccharomyces cerevisiae

2002 ◽  
Vol 66 (4) ◽  
pp. 579-591 ◽  
Author(s):  
José L. Crespo ◽  
Michael N. Hall
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Protein Kinase ◽  
Cell Growth ◽  
Anticancer Drug ◽  
Current Understanding ◽  
Target Of Rapamycin ◽  
Related Protein ◽  
Tor Signaling ◽  
Modes Of Action ◽  
Phosphatidylinositol Kinase

SUMMARY TOR (target of rapamycin) is a phosphatidylinositol kinase-related protein kinase that controls cell growth in response to nutrients. Rapamycin is an immunosuppressive and anticancer drug that acts by inhibiting TOR. The modes of action of TOR and rapamycin are remarkably conserved from S. cerevisiae to humans. The current understanding of TOR and rapamycin is derived largely from studies with S. cerevisiae. In this review, we discuss the contributions made by S. cerevisiae to understanding rapamycin action and TOR function.

scholarly journals MK5 haplodeficiency attenuates hypertrophy and preserves diastolic function during remodeling induced by chronic pressure overload in the mouse heart

2017 ◽  
Vol 313 (1) ◽  
pp. H46-H58 ◽  
Author(s):  
Sherin Ali Nawaito ◽  
Dharmendra Dingar ◽  
Pramod Sahadevan ◽  
Bahira Hussein ◽  
Fatiha Sahmi ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Diastolic Function ◽  
Collagen Type ◽  
Systolic Function ◽  
Pressure Overload ◽  
Myocardial Remodeling ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Collagen Type 1

MAPK-activated protein kinase-5 (MK5) is a protein serine/threonine kinase that is activated by p38 MAPK and the atypical MAPKs ERK3 and ERK4. The physiological function(s) of MK5 remains unknown. Here, we examined the effect of MK5 haplodeficiency on cardiac function and myocardial remodeling. At 12 wk of age, MK5 haplodeficient mice (MK5+/−) were smaller than age-matched wild-type littermates (MK5+/+), with similar diastolic function but reduced systolic function. Transverse aortic constriction (TAC) was used to induce chronic pressure overload in 12-wk-old male MK5+/− and MK5+/+ mice. Two weeks post-TAC, heart weight-to-tibia length ratios were similarly increased in MK5+/− and MK5+/+ hearts, as was the abundance of B-type natriuretic peptide and β-myosin heavy chain mRNA. Left ventricular ejection fraction was reduced in both MK5+/+ and MK5+/− mice, whereas regional peak systolic tissue velocities were reduced and isovolumetric relaxation time was prolonged in MK5+/+ hearts but not in MK5+/− hearts. The TAC-induced increase in collagen type 1-α1 mRNA observed in MK5+/+ hearts was markedly attenuated in MK5+/− hearts. Eight weeks post-TAC, systolic function was equally impaired in MK5+/+ and MK5+/− mice. In contrast, the increase in E wave deceleration rate and progression of hypertrophy observed in TAC MK5+/+ mice were attenuated in TAC MK5+/− mice. MK5 immunoreactivity was detected in adult fibroblasts but not in myocytes. MK5+/+, MK5+/−, and MK5−/− fibroblasts all expressed α-smooth muscle actin in culture. Hence, reduced MK5 expression in cardiac fibroblasts was associated with the attenuation of both hypertrophy and development of a restrictive filling pattern during myocardial remodeling in response to chronic pressure overload. NEW & NOTEWORTHY MAPK-activated protein kinase-5 (MK5)/p38-regulated/activated protein kinase is a protein serine/threonine kinase activated by p38 MAPK and/or the atypical MAPKs ERK3 and ERK4. MK5 immunoreactivity was detected in adult ventricular fibroblasts but not in myocytes. MK5 haplodeficiency attenuated the progression of hypertrophy, reduced collagen type 1 mRNA, and protected diastolic function in response to chronic pressure overload.

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