New insights into PKC family affairs: three novel phosphorylation sites in PKCϵ and at least one is regulated by PKCα

2008 ◽  
Vol 411 (2) ◽  
pp. e15-e16 ◽  
Author(s):  
Christer Larsson
Keyword(s):  
Phosphorylation Sites ◽  
Functional Importance ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Cellular Processes ◽  
Biochemical Journal ◽  
Pkc Isoforms ◽  
Evolutionarily Conserved ◽  
The Individual

PKCϵ (protein kinase Cϵ) is a serine/threonine kinase, and a member of the PKC family of isoforms. The different PKC isoforms regulate many cellular processes of importance for disease. It is therefore desirable to obtain tools to specifically modulate the activity of the individual isoforms and to develop markers of PKC activity. The paper by Durgan et al. in this issue of the Biochemical Journal has taken us some steps further towards these goals. In the paper they identify three previously unknown phosphorylation sites in PKCϵ. All of them are specific for the ϵ isoform, evolutionarily conserved and tightly regulated. The phosphorylation of one site is critical for the binding of PKCϵ to 14-3-3β, suggesting it is of functional importance. The results provide important novel findings that uncover new aspects of PKCϵ regulation and reveal new possibilities for detecting PKCϵ activity in situ.

The identification and characterization of novel PKCϵ phosphorylation sites provide evidence for functional cross-talk within the PKC superfamily

2008 ◽  
Vol 411 (2) ◽  
pp. 319-331 ◽  
Author(s):  
Joanne Durgan ◽  
Angus J. Cameron ◽  
Adrian T. Saurin ◽  
Sarah Hanrahan ◽  
Nick Totty ◽  
...  
Keyword(s):  
Cross Talk ◽  
Phosphorylation Sites ◽  
Serine Threonine Kinase ◽  
Cellular Processes ◽  
Mammalian Cell Lines ◽  
Pkc Isoforms ◽  
Broad Array ◽  
Cellular Context ◽  
In Trans

PKCϵ (protein kinase Cϵ) is a phospholipid-dependent serine/threonine kinase that has been implicated in a broad array of cellular processes, including proliferation, survival, migration, invasion and transformation. Here we demonstrate that, in vitro, PKCϵ undergoes autophosphorylation at three novel sites, Ser234, Ser316 and Ser368, each of which is unique to this PKC isoform and is evolutionarily conserved. We show that these sites are phosphorylated over a range of mammalian cell lines in response to a number of different stimuli. Unexpectedly, we find that, in a cellular context, these phosphorylation events can be mediated in-trans by cPKC (classical PKC) isoforms. The functional significance of this cross-talk is illustrated through the observation that the cPKC-mediated phosphorylation of PKCϵ at residue Ser368 controls an established PKCϵ scaffold interaction. Thus our current findings identify three new phosphorylation sites that contribute to the isoform-specific function of PKCϵ and highlight a novel and direct means of cross-talk between different members of the PKC superfamily.

GSK-3 Inhibitors in Regulation and Controlling of Colon Carcinoma

2021 ◽  
Vol 22 ◽  
Author(s):  
Sitansu Sekhar Nanda ◽  
Md Imran Hossain ◽  
Heongkyu Ju ◽  
Dong Kee Yi
Keyword(s):  
Colon Carcinoma ◽  
Clinical Studies ◽  
Glycogen Synthesis ◽  
Morphological Examination ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Cellular Processes ◽  
Adenocarcinoma Cells ◽  
Membrane Bound

Background: GSK-3 inhibitors became a novel therapeutic agent treating cancer. There are so many uses of GSK-3 inhibitor for treating cancer like breast cancer, lung cancer, gastric cancer, and no pathological changes are shown by the morphological examination of GSK-3. Objectives: This review describes the recent affairs using GSK-3 inhibitors, mainly treating in colon carcinoma. The authorsAuthors have also shown the different mechanisms of different GSK-3 inhibitors for treating various cancers and proposed some mechanisms that can be useful for further research by GSK-3 inhibitors for various cancerscancer including colon carcinoma. Results: The majority of the cancers and pre-cancerous lesions are stimulated by the transformation of membrane-bound arachidonic acid (AA) to eicosanoids for the viability, proliferation, and spread of cancer. GSK-3 inhibitors can reinstate hostility to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) responsiveness in gastric adenocarcinoma cells. GSK-3, the final enzyme in glycogen synthesis, is a serine/threonine kinase that phosphorylates varied sequences that are more than a hundred in number, within proteins in an array of heterogeneous pathways. It is an essential module of an exceptionally huge number of cellular processes, a fundamental role in many metabolic processes and diseases. Many patients achieve long term remission with outstanding survival diagnosed with colon cancer through it. Conclusion: Before the extensive application of these proposed mechanisms of GSK-3 inhibitor, further evaluation and clinical studies are needed. After doing the appropriate clinical studies and morphological examination, it can be appropriate for extensive application.

scholarly journals In Situ Hybridization Analysis of ZPK Gene Expression During Murine Embryogenesis

1997 ◽  
Vol 45 (1) ◽  
pp. 107-118 ◽  
Author(s):  
André Nadeau ◽  
Gilles Grondin ◽  
Richard Blouin
Keyword(s):  
In Situ Hybridization ◽  
Northern Blot Analysis ◽  
Spatial And Temporal Patterns ◽  
Serine Threonine Kinase ◽  
Teratocarcinoma Cell ◽  
Threonine Kinase ◽  
Cell Lineages ◽  
Polymerase Chain

ZPK is a recently described protein serine/threonine kinase that has been originally identified from a human teratocarcinoma cell line by the polymerase chain reaction and whose function in signal transduction has not yet been elucidated. To investigate the potential role of this protein kinase in developmental processes, we have analyzed the spatial and temporal patterns of expression of the ZPK gene in mouse embryos of different gestational ages. Northern blot analysis revealed a single mRNA species of about 3.5 KB from Day 11 of gestation onwards. In situ hybridization studies demonstrated strong expression of ZPK mRNA in brain and in a variety of embryonic organs that rely on epithelio-mesenchymal interactions for their development, including skin, intestine, pancreas, and kidney. In these tissues, the ZPK mRNA was localized primarily in areas composed of specific types of differentiating cells, and this expression appeared to be upregulated at a time concomitant with the onset of terminal differentiation. Taken together, these observations raise the possibility that the ZPK gene product is involved in the establishment and/or maintenance of a fully cytodifferentiated state in a variety of cell lineages.

scholarly journals Target of Rapamycin in Control of Autophagy: Puppet Master and Signal Integrator

2020 ◽  
Vol 21 (21) ◽  
pp. 8259
Author(s):  
Yosia Mugume ◽  
Zakayo Kazibwe ◽  
Diane C. Bassham
Keyword(s):  
Degradation Pathway ◽  
Target Of Rapamycin ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Photosynthetic Organisms ◽  
Downstream Effectors ◽  
Evolutionarily Conserved ◽  
Recent Developments ◽  
Stress Signals ◽  
And Function

The target of rapamycin (TOR) is an evolutionarily-conserved serine/threonine kinase that senses and integrates signals from the environment to coordinate developmental and metabolic processes. TOR senses nutrients, hormones, metabolites, and stress signals to promote cell and organ growth when conditions are favorable. However, TOR is inhibited when conditions are unfavorable, promoting catabolic processes such as autophagy. Autophagy is a macromolecular degradation pathway by which cells degrade and recycle cytoplasmic materials. TOR negatively regulates autophagy through phosphorylation of ATG13, preventing activation of the autophagy-initiating ATG1-ATG13 kinase complex. Here we review TOR complex composition and function in photosynthetic and non-photosynthetic organisms. We also review recent developments in the identification of upstream TOR activators and downstream effectors of TOR. Finally, we discuss recent developments in our understanding of the regulation of autophagy by TOR in photosynthetic organisms.

scholarly journals Relevance of STK11 Mutations Regarding Immune Cell Infiltration, Drug Sensitivity, and Cellular Processes in Lung Adenocarcinoma

2020 ◽  
Vol 10 ◽  
Author(s):  
Zhenqing Li ◽  
Bo Ding ◽  
Jianxun Xu ◽  
Kai Mao ◽  
Pengfei Zhang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Drug Sensitivity ◽  
Immune Cell ◽  
Differentially Expressed ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Wild Type ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Cellular Processes

Serine/threonine kinase 11 (STK11) is one member of the serine/threonine kinase family, which is involved in regulating cell polarity, apoptosis, and DNA damage repair. In lung adenocarcinoma (LUAD), it can play as one tumor suppressor and always be mutated. In this study, we aimed to assess the relevance of STK11 mutations in LUAD, in which we also studied the correlation among immune cell infiltration, drug sensitivity, and cellular processes. By performing the bioinformatics analysis of the Cancer Genome Atlas (TCGA) about LUAD patients, we found that the mutation efficiency of STK11 mutations is about 19%. Additionally, the differentially expressed gene analysis showed that there were 746 differentially expressed genes (DEGs) between LUAD patients with and without STK11 mutations. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis showed that the DEGs were enriched in various tumorigenesis signaling pathways and metabolic processes. Among these DEGs, the top ranking 21 genes were found that they were more frequently mutated in the STK11 mutation group than in the wild-type group (p-value<0.01). Finally, the LUAD patients with STK11 mutations suffered the worse immune cell infiltration levels than the LUAD patients with wild-type. The STK11 gene copy number was correlated with immune cell infiltration. Aiming to develop the therapeutic drugs, we performed Genomics of Drug Sensitivity in Cancer (GDSC) data to identify the potential therapeutic candidate and the results showed that Nutlin-3a(-) may be a sensitive drug for LUAD cases harboring STK11 mutations. The specific genes and pathways shown to be associated with LUAD cases involving STK11 mutations may serve as targets for individualized LUAD treatment.

scholarly journals PAS kinase: An evolutionarily conserved PAS domain-regulated serine/threonine kinase

2001 ◽  
Vol 98 (16) ◽  
pp. 8991-8996 ◽  
Author(s):  
J. Rutter ◽  
C. H. Michnoff ◽  
S. M. Harper ◽  
K. H. Gardner ◽  
S. L. McKnight
Keyword(s):  
Pas Domain ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Pas Kinase ◽  
Evolutionarily Conserved

scholarly journals Tyr198 is the Essential Autophosphorylation Site for STK16 Localization and Kinase Activity

2019 ◽  
Vol 20 (19) ◽  
pp. 4852 ◽  
Author(s):  
Junjun Wang ◽  
Juanjuan Liu ◽  
Xinmiao Ji ◽  
Xin Zhang
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Kinase Activity ◽  
Kinase Domain ◽  
Serine Threonine Kinase ◽  
Cycle Progression ◽  
Threonine Kinase ◽  
Cellular Processes ◽  
Activation Segment ◽  
And Function

STK16, reported as a Golgi localized serine/threonine kinase, has been shown to participate in multiple cellular processes, including the TGF-β signaling pathway, TGN protein secretion and sorting, as well as cell cycle and Golgi assembly regulation. However, the mechanisms of the regulation of its kinase activity remain underexplored. It was known that STK16 is autophosphorylated at Thr185, Ser197, and Tyr198 of the activation segment in its kinase domain. We found that STK16 localizes to the cell membrane and the Golgi throughout the cell cycle, but mutations in the auto-phosphorylation sites not only alter its subcellular localization but also affect its kinase activity. In particular, the Tyr198 mutation alone significantly reduced the kinase activity of STK16, abolished its Golgi and membrane localization, and affected the cell cycle progression. This study demonstrates that a single site autophosphorylation of STK16 could affect its localization and function, which provides insights into the molecular regulatory mechanism of STK16’s kinase activity.

X-ray structural studies of the entire extracellular region of the serine/threonine kinase PrkC from Staphylococcus aureus

2011 ◽  
Vol 435 (1) ◽  
pp. 33-41 ◽  
Author(s):  
Alessia Ruggiero ◽  
Flavia Squeglia ◽  
Daniela Marasco ◽  
Roberta Marchetti ◽  
Antonio Molinaro ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Serine Threonine Kinase ◽  
X Ray ◽  
Threonine Kinase ◽  
Extracellular Milieu ◽  
Cellular Processes ◽  
Extracellular Region ◽  
High Concentrations ◽  
Growing Conditions ◽  
Adhesive Proteins

Bacterial serine/threonine kinases modulate a wide number of cellular processes. The serine/threonine kinase PrkC from the human pathogen Staphylococcus aureus was also shown to induce germination of Bacillus subtilis spores, in response to cell wall muropeptides. The presence of muropeptides in the bacterial extracellular milieu is a strong signal that the growing conditions are promising. In the present paper, we report the X-ray structure of the entire extracellular region of PrkC from S. aureus. This structure reveals that the extracellular region of PrkC, EC-PrkC, is a linear modular structure composed of three PASTA (penicillin binding-associated and serine/threonine kinase-associated) domains and an unpredicted C-terminal domain, which presents the typical features of adhesive proteins. Using several solution techniques, we also found that EC-PrkC shows no tendency to dimerize even in the presence of high concentrations of muropeptides. X-ray structural results obtained in the present study provide molecular clues into the mechanism of muropeptide-induced PrkC activation.

scholarly journals CARMA1 Is Required for Akt-Mediated NF-κB Activation in T Cells

2006 ◽  
Vol 26 (6) ◽  
pp. 2327-2336 ◽  
Author(s):  
Preeti Narayan ◽  
Brittany Holt ◽  
Richard Tosti ◽  
Lawrence P. Kane
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Receptor ◽  
Functional Interaction ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Kinase C ◽  
Evolutionarily Conserved ◽  
The Common ◽  
Protein Kinase C Activation

ABSTRACT Many details of the generic pathway for induction of NF-κB have been delineated, but it is still not clear how multiple, diverse receptor systems are able to converge on this evolutionarily conserved family of transcription factors. Recent studies have shown that the CARMA1, Bcl10, and MALT1 proteins are critical for coupling the common elements of the NF-κB pathway to the T-cell receptor (TCR) and CD28. We previously demonstrated a role for the serine/threonine kinase Akt in CD28-mediated NF-κB induction. Using a CARMA1-deficient T-cell line, we have now found that the CARMA complex is required for induction of NF-κB by Akt, in cooperation with protein kinase C activation. Furthermore, using a novel selective inhibitor of Akt, we confirm that Akt plays a modulatory role in NF-κB induction by the TCR and CD28. Finally, we provide evidence for a physical and functional interaction between Akt and CARMA and for Akt-dependent phosphorylation of Bcl10. Therefore, in T cells, Akt impinges upon NF-κB signaling through at least two separate mechanisms.

TheMycobacterium tuberculosis serine/threonine kinase PknL phosphorylates Rv2175c: Mass spectrometric profiling of the activation loop phosphorylation sites and their role in the recruitment of Rv2175c

PROTEOMICS ◽  
2008 ◽  
Vol 8 (3) ◽  
pp. 521-533 ◽  
Author(s):  
Marc J. Canova ◽  
Romain Veyron-Churlet ◽  
Isabelle Zanella-Cleon ◽  
Martin Cohen-Gonsaud ◽  
Alain J. Cozzone ◽  
...  
Keyword(s):  
Mass Spectrometric ◽  
Activation Loop ◽  
Phosphorylation Sites ◽  
Serine Threonine Kinase ◽  
Threonine Kinase
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