No abstract available.
Humans* ; Keratinocytes* ; Protein-Serine-Threonine Kinases* ; Serine* ; Threonine*

Humans ; Phosphorylation ; Serine ; Protein Serine-Threonine Kinases/metabolism* ; Spasms, Infantile

Translationally controlled tumor proteins (TCTP) and SNF1- related protein kinase (SnRK1) are conserved and widely present in eukaryotic cells. TCTP regulates cell division, plant growth and development, and mediates plant resistance against pathogen infection. SnRK1 participates in a range of physiological processes including sugar metabolism and resistance to abiotic and biotic stresses. Previous work in our laboratory demonstrated that wheat TCTP can respond to Puccinia triticina infection and induce host defense responses. In order to further investigate the mechanism of TaTCTP in wheat resistance to Puccinia triticina infection, we used TAP (tandem affinity purification) and mass spectrometry to screen the potential interactants of TaTCTP. A SNF1- related protein kinase (SnRK1) was identified as a potential interacting protein of TaTCTP. The results of yeast two-hybrid assay showed that TCTP could interact with SnRK1 in yeast, and the yeast carrying TCTP and SnRK1 could grow on SD/-Leu/-Trp/-His/-Ade (SD/-LWHA) medium. The fluorescence signal of the interaction between TCTP and SnRK1 was found to be distributed in the cytoplasm in the Bi-fluorescense complementation experiment. Co-IP experiments further showed that TCTP and SnRK1 could interact in plant cells. This study lays an important foundation for further studying the mechanism of TaTCTP in the interaction between wheat and Puccinia triticina, and it play a great influence on further improving the molecular mechanism of wheat resistant to Puccinia triticina.
Basidiomycota ; Humans ; Neoplasms ; Protein Biosynthesis ; Protein-Serine-Threonine Kinases ; Triticum

Necroptosis is one of the regulated cell death, which involves receptor interacting protein kinase (RIPK) 1/RIPK3/mixed lineage kinase domain like protein (MLKL) signaling pathway. Among them, MLKL is the final execution of necroptosis. The formation of RIPK1/RIPK3/MLKL necrosome induces the phosphorylated MLKL, and the activated MLKL penetrates into the membrane bilayer to form membrane pores, which damages the integrity of the membrane and leads to cell death. In addition to participating in necroptosis, MLKL is also closely related to other cell death, such as NETosis, pyroptosis, and autophagy. Therefore, MLKL is involved in the pathological processes of various diseases related to abnormal cell death pathways (such as cardiovascular diseases, neurodegenerative diseases and cancer), and may be a therapeutic target of multiple diseases. Understanding the role of MLKL in different cell death can lay a foundation for seeking various MLKL-related disease targets, and also guide the development and application of MLKL inhibitors.
Protein Kinases/metabolism* ; Necroptosis/physiology* ; Receptor-Interacting Protein Serine-Threonine Kinases ; Signal Transduction ; Pyroptosis ; Apoptosis

Humans ; Phosphorylation ; Serine/metabolism* ; Protein Serine-Threonine Kinases/metabolism* ; Signal Transduction ; Neovascularization, Pathologic

Myotonic dystrophy type 1 (DM1), which is a dominantly inherited neurodegenerative disorder, results from a CTG trinucleotide repeat expansion in the 3'-untranslated region (3'-UTR) of the myotonic dystrophy protein kinase (DMPK) gene. Retention of mutant DMPK (mDMPK) transcripts in the nuclei of affected cells has been known to be the main cause of pathogenesis of the disease. Thus, reducing the RNA toxicity through elimination of the mutant RNA has been suggested as one therapeutic strategy against DM1. In this study, we suggested RNA replacement with a trans -splicing ribozyme as an alternate genetic therapeutic approach for amelioration of DM1. To this end, we identified the regions of mDMPK 3'-UTR RNA that were accessible to ribozymes by using an RNA mapping strategy based on a trans - splicing ribozyme library. We found that particularly accessible sites were present not only upstream but also downstream of the expanded repeat sequence. Repair or replacement of the mDMPK transcript with the specific ribozyme will be useful for DM1 treatment through reduction of toxic mutant transcripts and simultaneously restore wild-type DMPK or release nucleus-entrapped mDMPK transcripts to the cytoplasm.
Cytoplasm ; Myotonic Dystrophy ; Neurodegenerative Diseases ; Protein Kinases ; Protein-Serine-Threonine Kinases ; Retention (Psychology) ; RNA ; RNA, Catalytic ; Trinucleotide Repeat Expansion

No Abstract Available.
Protein-Serine-Threonine Kinases* ; Receptors, Cell Surface* ; Transforming Growth Factor beta*

BACKGROUND/AIMS: Signaling pathways via integrin-linked kinase (ILK) and beta-catenin are important in the initiation and progression of various malignant diseases. ILK modulates the transcription of beta-catenin and is implicated in cell migration and invasiveness. Recently, premalignant colon polyps were found to express ILK and beta-catenin. Therefore, we investigated the expression of ILK and beta-catenin in colon polyps according to the gross morphology and pathologic type. METHODS: Based on morphology, colon polyps (62) were classified as being a pedunculated polyp (Ip, 16), sessile polyp (Is, 22), or laterally spreading tumor (LST, 24). The colon polyps were classified pathologically as tubular adenomas (TAs, 47) and hyperplastic polyps (HPs, 15). The expression levels of ILK and beta-catenin in colon polyps and normal colon (6) were evaluated with immunohistochemistry. RESULTS: In normal colon, ILK was not expressed, and beta-catenin stained in the cell membrane only. Based on the gross morphology of the colon polyps, no significant difference was seen in the expression of ILK and beta-catenin (p>0.05). The expression of both ILK and beta-catenin in TAs was greater than that in HPs (p<0.01): the greater the dysplasia in TAs, the more both ILK and beta-catenin were expressed (p<0.05). The grade of expression of ILK was correlated with that of beta-catenin in colon polyps (p<0.01). CONCLUSIONS: The expression of ILK and beta-catenin did not differ according to the morphology of colon polyps, but was expressed more in TAs than in HPs, especially in severe dysplasia.
Adenoma ; beta Catenin ; Cell Membrane ; Cell Movement ; Colon ; Immunohistochemistry ; Phosphotransferases ; Polyps ; Protein-Serine-Threonine Kinases ; Proteins

BACKGROUNDPeutz-Jeghers syndrome (PJS) is an autosomal dominantly inherited disease. STK11/LKB1 gene germline mutations have been identified as responsible for PJS. In our study, we investigated the molecular basis of PJS and evaluated correlation between the STK11 mutations and the Chinese population.

METHODSWe collected three pedigrees of PJS and screened the 9 exons and their flanking intronic sequences of STK11/LKB1 gene in the probands and normal individuals in the families using polymerase chain reaction (PCR) and direct sequencing.

RESULTSSequencing of the STK11 gene in the probands of 3 families revealed two novel mutations (c180C-->G and c998-1002delGCAGC) in exon 1 and exon 8, respectively. The mutation of c180C-->G resulted in a premature termination codon. The other mutation, a deletion of five nucleotides (998-1002delGCAGC) in exon 8, predicted to generate a translational frameshift and a termination at codon 1070.

CONCLUSIONSThe growing number of mutations in PJS pedigrees suggests the molecular basis of PJS. STK11 gene mutation can be detected in most patients with PJS.

Child ; Female ; Humans ; Male ; Mutation ; Pedigree ; Peutz-Jeghers Syndrome ; genetics ; Protein-Serine-Threonine Kinases ; genetics

OBJECTIVETo determine the effect of type I transmembrane protein (IRE1alpha) deletions on the cell cycle of human periodontal ligament fibroblasts (hPDLFs) cells.

METHODSBased on the IRE1alpha deletions, a full-length model was successfully constructed. Moreover, overlapping polymerase chain reaction mutagenesis facilitated the establishment of two deletion mutants of IREla (pD-Kinase, pD-Rnase). The full-length model and two mutant eukaryotic expression vectors were transfected into hPDLFs cells. Western blot analysis was performed to identify the expression in the cells. The changes in the cell cycle of hPDLFS cells were detected by flow cytometry (FCM).

RESULTSThe two deletion mutants of IRE1alpha with eukaryotic expression vectors were successfully constructed and correctly expressed in hPDLFs cells based on Western blot analysis. Under stress conditions, the FCM assay showed that cell percentage of S phases increased, whereas that of G1 phases decreased in the IRE1alpha group (P < 0.05) compared with the control group of tunicamycin (TM) treatment. Moreover, the cell percentage of the S phases decreased, whereas that of the G1 phases increased in the D-Rnase group (P < 0.05) compared with the control. The deletion mutant D-Kinase had no influence on hPDLFS cell proliferation and cycle (P>0.05).

CONCLUSIONUnder stress conditions, IRE1alpha can improve the cell cycle of hPDLFs cells from the G1 to the S phase. The deletion mutant D-Rnase cause hPDLFs cell growth arrest at the G1 phase, whereas deletion mutant D-Kinase has no significant effect.

Cell Cycle ; Cell Proliferation ; Endoribonucleases ; Fibroblasts ; Humans ; Periodontal Ligament ; Protein-Serine-Threonine Kinases ; Transfection