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 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.

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.

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.

scholarly journals Damage Tolerance Protein Mus81 Associates with the FHA1 Domain of Checkpoint Kinase Cds1

2000 ◽  
Vol 20 (23) ◽  
pp. 8758-8766 ◽  
Author(s):  
Michael N. Boddy ◽  
Antonia Lopez-Girona ◽  
Paul Shanahan ◽  
Heidrun Interthal ◽  
Wolf-Dietrich Heyer ◽  
...  
Keyword(s):  
Damage Tolerance ◽  
Excision Repair ◽  
Protein Docking ◽  
Serine Threonine Kinase ◽  
Dna Structures ◽  
Threonine Kinase ◽  
Repair Protein ◽  
Nucleotide Excision ◽  
Evolutionarily Conserved ◽  
Genetic Epistasis

ABSTRACT Cds1, a serine/threonine kinase, enforces the S-M checkpoint in the fission yeast Schizosaccharomyces pombe. Cds1 is required for survival of replicational stress caused by agents that stall replication forks, but how Cds1 performs these functions is largely unknown. Here we report that the forkhead-associated-1 (FHA1) protein-docking domain of Cds1 interacts with Mus81, an evolutionarily conserved damage tolerance protein. Mus81 has an endonuclease homology domain found in the XPF nucleotide excision repair protein. Inactivation of mus81 reveals a unique spectrum of phenotypes. Mus81 enables survival of deoxynucleotide triphosphate starvation, UV radiation, and DNA polymerase impairment. Mus81 is essential in the absence of Bloom's syndrome Rqh1 helicase and is required for productive meiosis. Genetic epistasis studies suggest that Mus81 works with recombination enzymes to properly replicate damaged DNA. Inactivation of Mus81 triggers a checkpoint-dependent delay of mitosis. We propose that Mus81 is involved in the recruitment of Cds1 to aberrant DNA structures where Cds1 modulates the activity of damage tolerance enzymes.

scholarly journals Targeted Inhibition of mTOR Signaling Improves Sensitivity of Esophageal Squamous Cell Carcinoma Cells to Cisplatin

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Guiqin Hou ◽  
Shuai Yang ◽  
Yuanyuan Zhou ◽  
Cong Wang ◽  
Wen Zhao ◽  
...  
Keyword(s):  
Cell Number ◽  
Carcinoma Cells ◽  
Serine Threonine Kinase ◽  
Western Blots ◽  
Threonine Kinase ◽  
Evolutionarily Conserved ◽  
Targeted Inhibition ◽  
Proliferation In Vitro

mTOR is an evolutionarily conserved serine-threonine kinase with a central role in cell growth, invasion, and metastasis of tumors, and is activated in many cancers. The aims of this study were to investigate the expression of mTOR in ESCC tissues and its relationship with progression of ESCC and measure the changes of sensitivity of ESCC cells to cisplatin after cells were treated with mTOR siRNA by WST-8 assays, TUNEL, RT-PCR, and western blots in vitro and in vivo. The results showed that the expression of mTOR was higher in ESCC specimens than that in normal esophageal tissues and its expression was closely correlated with the TNM stage of ESCC. mTOR siRNA significantly increased the sensitivity of the EC9706 cells to cisplatin at proliferation in vitro and in vivo. The growth of ESCC xenografts was significantly inhibited by mTOR siRNA or cisplatin, and the cell number of apoptosis was obviously increased after xenografts were treated with mTOR siRNA or cisplatin alone, especially when mTOR siRNA combined with cisplatin. The present study demonstrates that the expression of mTOR has important clinical significance and inhibition of mTOR pathway by mTOR siRNA can improve the sensitivity of ESCC cells to cisplatin.

scholarly journals Maternal Nanos represses hid/skl-dependent apoptosis to maintain the germ line in Drosophila embryos

2007 ◽  
Vol 104 (18) ◽  
pp. 7455-7460 ◽  
Author(s):  
Kimihiro Sato ◽  
Yoshiki Hayashi ◽  
Yuichi Ninomiya ◽  
Shuji Shigenobu ◽  
Kayo Arita ◽  
...  
Keyword(s):  
Germ Line ◽  
Primordial Germ Cells ◽  
Critical Event ◽  
Caspase Activation ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Evolutionarily Conserved ◽  
Regulated Expression ◽  
Pole Cells ◽  
Drosophila Embryos

Nanos (Nos) is an evolutionarily conserved protein essential for the survival of primordial germ cells. In Drosophila, maternal Nos partitions into pole cells and suppresses apoptosis to permit proper germ-line development. However, how this critical event is regulated by Nos has remained elusive. Here, we report that Nos represses apoptosis of pole cells by suppressing translation of head involution defective (hid), a member of the RHG gene family that is required for Caspase activation. In addition, we demonstrate that hid acts in concert with another RHG gene, sickle (skl), to induce apoptosis. Expression of skl is induced in pole cells by maternal tao-1, a ste20-like serine/threonine kinase. Tao-1-dependent skl expression is required to potentiate hid activity. However, skl expression is largely suppressed in normal pole cells. Once the pole cells lack maternal Nos, Tao-1-dependent skl expression is fully activated, suggesting that skl expression is also restricted by Nos. These findings provide the first evidence that the germ line is maintained through the regulated expression of RHG genes.

scholarly journals mTOR Pathways in Cancer and Autophagy

Cancers ◽  
2018 ◽  
Vol 10 (1) ◽  
pp. 18 ◽  
Author(s):  
Mathieu Paquette ◽  
Leeanna El-Houjeiri ◽  
Arnim Pause
Keyword(s):  
Cell Death ◽  
Cell Growth ◽  
Signaling Pathways ◽  
Molecular Level ◽  
Clinical Implications ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Evolutionarily Conserved ◽  
Stress Signals ◽  
The Relationship

TOR (target of rapamycin), an evolutionarily-conserved serine/threonine kinase, acts as a central regulator of cell growth, proliferation and survival in response to nutritional status, growth factor, and stress signals. It plays a crucial role in coordinating the balance between cell growth and cell death, depending on cellular conditions and needs. As such, TOR has been identified as a key modulator of autophagy for more than a decade, and several deregulations of this pathway have been implicated in a variety of pathological disorders, including cancer. At the molecular level, autophagy regulates several survival or death signaling pathways that may decide the fate of cancer cells; however, the relationship between autophagy pathways and cancer are still nascent. In this review, we discuss the recent cellular signaling pathways regulated by TOR, their interconnections to autophagy, and the clinical implications of TOR inhibitors in cancer.

scholarly journals Quantitative Phosphoproteomic Analyses Identify STK11IP as a Lysosome-Specific Substrate of mTORC1 that Regulates Lysosomal Acidification

2021 ◽  
Author(s):  
Zhenzhen Zi ◽  
Zhuzhen Zhang ◽  
Qiang Feng ◽  
Chiho Kim ◽  
Philipp E. Scherer ◽  
...  
Keyword(s):  
Specific Substrate ◽  
Serine Threonine Kinase ◽  
Deficient Diet ◽  
Threonine Kinase ◽  
Promising Therapeutic Target ◽  
Evolutionarily Conserved ◽  
Cell Growth And Proliferation ◽  
Lysosomal Acidification ◽  
Lysosomal Proteins

The evolutionarily conserved serine/threonine kinase mTORC1 is a central regulator of cell growth and proliferation. mTORC1 is activated on the lysosome surface. However, once mTORC1 is activated, it is unclear whether mTORC1 phosphorylates local lysosomal proteins to regulate specific aspects of lysosomal biology. Through cross-reference analyses of lysosome proteomic with mTORC1-regulated phosphoproteomic, we identified STK11IP as a novel lysosome-specific substrate of mTORC1. mTORC1 directly phosphorylates STK11IP at S404. Knockout of STK11IP led to a robust increase of autophagosome-lysosome fusion and autophagy flux. Dephosphorylation of STK11IP at S404 represses the role of STK11IP as an autophagy inhibitor. Mechanistically, STK11IP binds to V-ATPase, and regulates the activity of V-ATPase. Knockout of STK11IP protects mice from fasting and Methionine-Choline-Deficient Diet (MCD) diet induced fatty liver. Thus, our study demonstrates that STK11IP phosphorylation represents a novel mechanism for mTORC1 to regulate lysosomal acidification, and points to STK11IP as a promising therapeutic target for the amelioration of diseases with aberrant autophagy signaling.

scholarly journals Autoregulation of the Raf-1 serine/threonine kinase

1998 ◽  
Vol 95 (16) ◽  
pp. 9214-9219 ◽  
Author(s):  
Richard E. Cutler ◽  
Robert M. Stephens ◽  
Misty R. Saracino ◽  
Deborah K. Morrison
Keyword(s):  
Plasma Membrane ◽  
Protein Kinase C ◽  
Regulatory Region ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Rich Domain ◽  
Kinase C ◽  
Evolutionarily Conserved ◽  
Phosphorylation Event ◽  
Cysteine Rich Domain

The Raf-1 serine/threonine kinase is a key protein involved in the transmission of many growth and developmental signals. In this report, we show that autoinhibition mediated by the noncatalytic, N-terminal regulatory region of Raf-1 is an important mechanism regulating Raf-1 function. The inhibition of the regulatory region occurs, at least in part, through binding interactions involving the cysteine-rich domain. Events that disrupt this autoinhibition, such as mutation of the cysteine-rich domain or a mutation mimicking an activating phosphorylation event (Y340D), alleviate the repression of the regulatory region and increase Raf-1 activity. Based on the striking similarites between the autoregulation of the serine/threonine kinases protein kinase C, Byr2, and Raf-1, we propose that relief of autorepression and activation at the plasma membrane is an evolutionarily conserved mechanism of kinase regulation.

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