scholarly journals A Novel Membrane Protein-Specific Serine/Threonine Kinase: Tissue Distribution and Role in Sperm Maturation

ISRN Urology ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-7
Author(s):  
Debjani Nath ◽  
Arpita Bhoumik ◽  
Sujoy Das ◽  
Debdas Bhattacharyya ◽  
Sandhya R. Dungdung ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Membrane Protein ◽  
The Novel ◽  
Serine Threonine Kinase ◽  
Membrane Biology ◽  
Threonine Kinase ◽  
Apparent Homogeneity ◽  
Sperm Membrane ◽  
First Time ◽  
Specific Membrane

Our recent studies have described for the first time the purification of an ectoprotein kinase to apparent homogeneity using caprine sperm as the model. Purified ectokinase (CIK) is a novel membrane protein-specific kinase that phosphorylates serine and threonine residues of ectophosphoproteins. This study, using ELISA based on ecto-CIK antibody demonstrates that ecto-CIK level is remarkably higher in the sperm membrane than in the cytosol. The epididymal sperm maturational event as well as sperm vertical velocity is associated with a significant increase in the ecto-CIK level. Ecto-CIK, the membrane protein-specific kinase, is also present in all the tissues tested and is predominantly localized in the cell membrane. Ubiquitous localization of the novel kinase on the mammalian cell membrane suggests that the kinase may play pivotal role in gamete as well as somatic cell regulation by modulating membrane biology through serine/threonine phosphorylation of specific membrane proteins located in the ectodomains.

scholarly journals MiR-9-5p Inhibits the Proliferation, Migration and Invasion of Choroidal Melanoma by Targeting BRAF

2020 ◽  
Vol 19 ◽  
pp. 153303382095698
Author(s):  
Manman Ying ◽  
Hao Feng ◽  
Xiaonan Zhang ◽  
Ran Liu ◽  
Hong Ning
Keyword(s):  
Western Blot ◽  
Mapk Pathway ◽  
Choroidal Melanoma ◽  
Target Prediction ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Transwell Assay ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
First Time

Objective: According to different reports, miR-9-5p either facilitates or suppresses the occurrence of tumors. BRAF is a serine/threonine kinase involved in the MAPK pathway and is a proto-oncogene promoting the progression of many tumors, especially melanoma. The present study aimed to reveal the mechanism of action of miR-9-5p and BRAF in choroidal melanoma (CM). Methods: RT-qPCR was used to detect the expression of miR-9-5p in CM cells after transfection with miR-9-5p mimics and inhibitor. EdU assay and Transwell assay, respectively, showed the proliferation, migration and invasion of CM cells after transfection with miR-9-5p mimics and inhibitor. A bioinformatics website was used for target prediction and the dual luciferase reporter assay was used to verify the interaction between miR-9-5p and BRAF. RT-qPCR and Western blot were performed to examine the expression of BRAF mRNA and protein, respectively. The BRAF protein was knocked down by siRNAs and then examined by Western blot. The effects of BRAF in CM cells were investigated by EdU assay and Transwell assay. Overexpressing BRAF and transfecting miR-9-5p mimics into choroidal melanoma cells confirmed the interaction between miR-9-5p and BRAF. Results: miR-9-5p could bind to the BRAF mRNA 3’UTR and inhibit the transcription and translation of BRAF, thereby suppressing the proliferation, migration and invasion of CM cell lines. Moreover, silencing BRAF inhibited the progression of CM cells. Conclusions: In conclusion, this study is the first to investigate the association among BRAF, miR-9-5p and the progression of CM cells. In addition, the interaction between BRAF and miR-9-5p was explored for the first time in CM. Thus, our study suggests that miR-9-5p, BRAF and their interaction may act as potential therapeutic targets for CM.

scholarly journals Design of Amino Acid- and Carbohydrate-Based Anticancer Drugs to Inhibit PIM kinases, an In Silico Study

2021 ◽  
Author(s):  
Sepideh Kalhor ◽  
Alireza Fattahi
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
The Novel ◽  
Serine Threonine Kinase ◽  
Cycle Progression ◽  
Threonine Kinase ◽  
Pim Kinases ◽  
In Silico Study ◽  
Regulation Of Cell Cycle ◽  
Cancerous Cells

PIM-1 is a serine-threonine kinase which is mainly expressed in tissues such as Thymus, spleen, bone marrow, and liver. This protein takes a role in many stages of the cell cycle, including the regulation of cell cycle progression and apoptosis. According to many studies, overexpression of PIM kinases happens in various types of human tumors; such as lymphomas, prostate cancer, and oral cancer. As a result, the design of drugs to inhibit PIM-1 in cancerous cells has attracted many attentions in recent years. This study aimed to design the alternative inhibitors for PIM-1 kinase, which are based on carbohydrates and amino acids and are expected to be non-toxic and to have the same chemotherapeutic effects as the traditional agents. The combinatorial use of quantum mechanics studies and molecular dynamic simulation (MD) has enabled us to precisely predict the mechanism of the inhibition of PIM-1 kinase by the novel designed drugs and to compare them with the recently synthesized chemotherapeutic drugs; such as DBC.

scholarly journals WD 40 domain of RqkA regulates its kinase activity and role in extraordinary radioresistance in Deinococcus radiodurans

2020 ◽  
Author(s):  
Dhirendra Kumar Sharma ◽  
Subhash C. Bihani ◽  
Hari S Misra ◽  
Yogendra S. Rajpurohit
Keyword(s):  
Dna Damage ◽  
Kinase Activity ◽  
Deinococcus Radiodurans ◽  
Serine Threonine Kinase ◽  
Γ Radiation ◽  
Threonine Kinase ◽  
Wd40 Domain ◽  
First Time

SummaryRqkA, a DNA damage responsive Serine / Threonine kinase is characterized for its role in DNA repair and cell division in D. radiodurans. It has a unique combination of a kinase domain at N-terminus and a WD40 type domain at C-terminus joined through a linker. WD40 domain is comprised of eight β propeller repeats held together via “tryptophan-docking motifs” and forming a typical ‘velcro’ closure structure. RqkA mutants lacking the WD40 region (hereafter referred to as WD mutant) could not complement RqkA loss in γ radiation resistance in D. radiodurans and lacked γ radiation mediated activation of kinase activity in vivo. WD mutants failed to phosphorylate its cognate substrate (e.g. DrRecA) in surrogate E. coli cells. Further, unlike wild type enzyme, the kinase activity of its WD40 mutants was not stimulated by Pyrroloquinoline quinine (PQQ) indicating the role of the WD motifs in PQQ interaction and stimulation of its kinase activity. Together, results highlighted the importance of the WD40 domain in the regulation of RqkA kinase signaling functions in vivo and thus the role of WD40 domain in the regulation of any STPK is the first time demonstrated in bacteria.ImportanceThis study highlights the importance of the WD40 domain in activity regulation and signaling activity of bacterial serine/ threonine kinase for the first time in the bacterial response to gamma radiation and DNA damage.

scholarly journals The novel membrane protein Hoka regulates septate junction organization and stem cell homeostasis in the Drosophila gut

2021 ◽  
Vol 134 (6) ◽  
Author(s):  
Yasushi Izumi ◽  
Kyoko Furuse ◽  
Mikio Furuse
Keyword(s):  
Stem Cell ◽  
Membrane Protein ◽  
Intestinal Barrier ◽  
Septate Junction ◽  
The Novel ◽  
Barrier Dysfunction ◽  
Cell Homeostasis ◽  
Extracellular Region ◽  
Membrane Spanning ◽  
Specific Membrane

ABSTRACT Smooth septate junctions (sSJs) regulate the paracellular transport in the intestinal tract in arthropods. In Drosophila, the organization and physiological function of sSJs are regulated by at least three sSJ-specific membrane proteins: Ssk, Mesh and Tsp2A. Here, we report a novel sSJ membrane protein, Hoka, which has a single membrane-spanning segment with a short extracellular region, and a cytoplasmic region with Tyr-Thr-Pro-Ala motifs. The larval midgut in hoka mutants shows a defect in sSJ structure. Hoka forms a complex with Ssk, Mesh and Tsp2A, and is required for the correct localization of these proteins to sSJs. Knockdown of hoka in the adult midgut leads to intestinal barrier dysfunction and stem cell overproliferation. In hoka-knockdown midguts, aPKC is upregulated in the cytoplasm and the apical membrane of epithelial cells. The depletion of aPKC and yki in hoka-knockdown midguts results in reduced stem cell overproliferation. These findings indicate that Hoka cooperates with the sSJ proteins Ssk, Mesh and Tsp2A to organize sSJs, and is required for maintaining intestinal stem cell homeostasis through the regulation of aPKC and Yki activities in the Drosophila midgut.

Structural requirements for subcellular localisation of the novel serine threonine kinase PKD2 in human gastric cancer cells

2003 ◽  
Vol 124 (4) ◽  
pp. A295-A296
Author(s):  
Thomas Seufferlein ◽  
Michael Beil ◽  
Schunter Marco ◽  
Wilhelm Schneiderhan ◽  
Alexandra Auer ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Subcellular Localisation ◽  
Human Gastric Cancer ◽  
The Novel ◽  
Gastric Cancer Cells ◽  
Serine Threonine Kinase ◽  
Structural Requirements ◽  
Threonine Kinase

scholarly journals The serine/threonine kinase PknB of Mycobacterium tuberculosis phosphorylates PBPA, a penicillin-binding protein required for cell division

Microbiology ◽  
2006 ◽  
Vol 152 (2) ◽  
pp. 493-504 ◽  
Author(s):  
Arunava Dasgupta ◽  
Pratik Datta ◽  
Manikuntala Kundu ◽  
Joyoti Basu
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Cell Division ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Peptidoglycan Biosynthesis ◽  
Division Site ◽  
Class B ◽  
First Time

A cluster of genes encoded by ORFs Rv0014c–Rv0018c in Mycobacterium tuberculosis encodes candidate cell division proteins RodA and PBPA, a pair of serine/threonine kinases (STPKs), PknA and PknB, and a phosphatase, PstP. The organization of genes encompassing this region is conserved in a large number of mycobacterial species. This study demonstrates that recombinant PBPA of M. tuberculosis binds benzylpenicillin. Knockout of its counterpart in M. smegmatis resulted in hindered growth and defective cell septation. The phenotype of the knockout (PBPA-KO) could be restored to that of the wild-type upon expression of PBPA of M. tuberculosis. PBPA localized to the division site along with newly synthesized peptidoglycan, between segregated nucleoids. In vivo coexpression of PBPA and PknB, in vitro kinase assays and site-specific mutagenesis substantiated the view that PknB phosphorylates PBPA on T362 and T437. A T437A mutant could not complement PBPA-KO. These studies demonstrate for the first time that PBPA, which belongs to a subclass of class B high-molecular-mass PBPs, plays an important role in cell division and cell shape maintenance. Signal transduction mediated by PknB and PstP likely regulates the positioning of this PBP at the septum, thereby regulating septal peptidoglycan biosynthesis.

The novel type I serine–threonine kinase receptor Alk8 binds TGF-β in the presence of TGF-βRII

2002 ◽  
Vol 293 (5) ◽  
pp. 1556-1565 ◽  
Author(s):  
Mark P de Caestecker ◽  
Martyn Bottomley ◽  
Sucharita Bhattacharyya ◽  
Tracie L Payne ◽  
Anita B Roberts ◽  
...  
Keyword(s):  
Type I ◽  
The Novel ◽  
Serine Threonine Kinase ◽  
Threonine Kinase

scholarly journals The StkP/PhpP Signaling Couple in Streptococcus pneumoniae: Cellular Organization and Physiological Characterization

2009 ◽  
Vol 191 (15) ◽  
pp. 4943-4950 ◽  
Author(s):  
Makoto Osaki ◽  
Tania Arcondéguy ◽  
Amandine Bastide ◽  
Christian Touriol ◽  
Hervé Prats ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Direct Interaction ◽  
Kinase Domain ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Physiological Characterization ◽  
Periplasmic Localization ◽  
Histidine Phosphorylation ◽  
First Time

ABSTRACT In Streptococcus pneumoniae, stkP and phpP, encoding the eukaryotic-type serine-threonine kinase and PP2C phosphatase, respectively, form an operon. PhpP has the features of a so-called “soluble” protein, whereas StkP protein is membrane associated. Here we provide the first genetic and physiological evidence that PhpP and StkP, with antagonist enzymatic activities, constitute a signaling couple. The StkP-PhpP couple signals competence upstream of the competence-specific histidine kinase ComD, receptor for the oligopeptide pheromone “competence stimulating peptide.” We show that PhpP activity is essential in a stkP + genetic background, suggesting tight control of StkP activity by PhpP. Proteins PhpP and StkP colocalized to the cell membrane subcellular fraction and likely belong to the same complex, as revealed by coimmunoprecipitation in cellular extracts. Specific coimmunoprecipitation of the N-kinase domain of StkP and PhpP recombinant proteins by PhpP-specific antibodies demonstrates direct interaction between these proteins. Consistently, flow cytometry analysis allowed the determination of the cytoplasmic localization of PhpP and of the N-terminal kinase domain of StkP, in contrast to the periplasmic localization of the StkP C-terminal PASTA (penicillin-binding protein and serine-threonine kinase associated) domain. A signaling route involving interplay between serine, threonine, and histidine phosphorylation is thus described for the first time in this human pathogen.

Abstract 40: Discovery and Characterization of the Novel Muscle-Specific Membrane Protein Smco1

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
James B Papizan ◽  
John R McAnally ◽  
Rhonda Bassel-Duby ◽  
Eric N Olson
Keyword(s):  
Skeletal Muscle ◽  
Membrane Proteins ◽  
Membrane Protein ◽  
Striated Muscle ◽  
Coiled Coil ◽  
Postnatal Growth ◽  
The Novel ◽  
And Function ◽  
Specific Membrane

Mutations in numerous membrane proteins cause debilitating myopathies. The discovery of novel muscle-specific, membrane proteins would likely provide insight into mechanisms of disease and potentially yield new therapeutic targets. Through bioinformatics screening for muscle-specific membrane proteins with unknown function, we identified C3orf43 or single-pass membrane protein with coiled-coil domains 1 (Smco1). Consistent with bioinformatics predictions, Smco1 is expressed exclusively in cardiac and skeletal muscle. We demonstrate with chromatin immunoprecipitation and luciferase promoter assays that Smco1 is a Mef2-regulated gene with robust expression occurring shortly after birth. Immunofluorescent analysis demonstrates Scmo1 localizes to the cardiomyocyte sarcolemma and intercalated disks. Talen-mediated disruption of Smco1 in mice results in stunted postnatal growth, cardiac hypoplasia and skeletal muscle myopathy as early as postnatal day 15. While studies are on going to determine the function of Smco1, our findings reveal an essential role of Smco1 in striated muscle structure and function. The identification of heart- and muscle-specific membrane proteins will likely illuminate the mechanisms of muscular membrane diseases.

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