Functional implication of human serine/threonine kinase, hAIK, in cell cycle progression

2000 ◽  
Vol 7 (6) ◽  
pp. 484-493 ◽  
Author(s):  
Shun-Chun Yang ◽  
Chian-Hoang Huang ◽  
Nien-Jung Chen ◽  
Cheng-Kung Chou ◽  
Chi-Hung Lin
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Serine Threonine Kinase ◽  
Cycle Progression ◽  
Functional Implication ◽  
Threonine Kinase

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.

Multiple Myeloma Cells Survival and Proliferation Rely on High Levels and Activity of the Serine-Threonine Kinase CK2.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 643-643 ◽  
Author(s):  
Francesco A. Piazza ◽  
Maria Ruzzene ◽  
Giovanni Di Maira ◽  
Enrico Brunetta ◽  
Luca Bonanni ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Transcriptional Activity ◽  
Kinase Activity ◽  
Serine Threonine Kinase ◽  
Cycle Progression ◽  
Threonine Kinase ◽  
Protein Levels ◽  
Tnf Α ◽  
Ck2 Inhibitors

Abstract Survival and proliferation of Multiple Myeloma plasma cells (MMPCs) depend on the activation of signaling pathways through the interaction with the surrounding bone marrow microenvironment. CK2 is a ubiquitous cellular serine-threonine kinase, whose involvement in oncogenic transformation, apoptosis and cell cycle progression has recently become matter of intense research. Due to its connection with signaling molecules pivotal for plasma cell (PCs) survival, such as those implicated in the TNF-α/NF-κB, IGF1/PI3K/AKT and Wnt/β-catenin pathways, CK2 is likely to play a central role in MM biology. We investigated CK2 function in MMPCs survival and cell cycle progression, in the modulation of the sensitivity to chemotherapeutics and in the regulation of the I-κB/NF-κB dependent pathway. We first analysed the CK2 protein levels and specific kinase activity in MMPCs. Different cell lines and highly purified CD138+ PCs from 5 patients were used. We observed higher protein levels of the CK2 catalytic subunit αin the neoplastic MMPCs than in controls (resting peripheral blood and splenic B lymphocytes). Moreover, also the total CK2-dependent kinase activity was found significantly increased in MMPCs. We also assessed the levels and pattern of total protein phosphorylation by radioactive phosphate incorporation assay. We found that MMPCs share a similar pattern of phoshorylated proteins. The degree of phosphorylation of some of these proteins was significantly reduced in the presence of specific CK2 inhibitors. Next, using a panel of highly specific CK2 inhibitors, we studied the effects of hampering CK2 function in MMPCs. A dose-dependent cytotoxic effect was observed after the treatment with such compounds that was associated with the activation of both the extrinsic and intrinsic caspase-dependent pathways, the release from mitochondria of cytochrome c and smac/diablo and cell cycle arrest in G2-M. A possible role for CK2 inhibition in sensitising MMPCs to melphalan-induced apoptosis was also investigated. Indeed, CK2 blockade lowered the threshold of sensitivity of MMPCs to the cytotoxic effect of melphalan. We then looked at the consequences of CK2 blockade on the NF-κB dependent signaling cascade. Basal and TNF-α-dependent I-κB-αdegradation, as well as NF-κB transcriptional activity upon TNF-αstimulation, were partially impaired by CK2 blockade in MMPCs. Finally, we detected association between the endogenous αcatalytic subunit of CK2 and the NF-κB p50/p105 member by confocal microscopy and co-immunoprecipitation. Altogether, our data suggest a pivotal role for CK2 in controlling survival, proliferation and sensitivity to chemotherapeutics of MMPCs and implicate this kinase in the regulation of the NF-κB pathway in MM through the modulation of I-κB protein levels and NF-κB transcriptional activity. This latter effect is possibly exerted through physical association of CK2 with NF-κB transcription factors. Our findings also suggest that CK2 inhibition could be exploited as a novel therapeutic approach for MM.

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 The Serine/Threonine Kinase Nek6 Is Required for Cell Cycle Progression through Mitosis

2003 ◽  
Vol 278 (52) ◽  
pp. 52454-52460 ◽  
Author(s):  
Min-Jean Yin ◽  
Lihua Shao ◽  
David Voehringer ◽  
Tod Smeal ◽  
Bahija Jallal
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Serine Threonine Kinase ◽  
Cycle Progression ◽  
Threonine Kinase

scholarly journals Akt/Protein Kinase B-Dependent Phosphorylation and Inactivation of WEE1Hu Promote Cell Cycle Progression at G2/M Transition

2005 ◽  
Vol 25 (13) ◽  
pp. 5725-5737 ◽  
Author(s):  
Kazuhiro Katayama ◽  
Naoya Fujita ◽  
Takashi Tsuruo
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Kinase Inhibitor ◽  
Phosphorylation Site ◽  
Cytoplasmic Localization ◽  
M Cell ◽  
Serine Threonine Kinase ◽  
Cycle Progression ◽  
M Phase ◽  
Promote Cell Cycle Progression

ABSTRACT The serine/threonine kinase Akt is known to promote cell growth by regulating the cell cycle in G1 phase through activation of cyclin/Cdk kinases and inactivation of Cdk inhibitors. However, how the G2/M phase is regulated by Akt remains unclear. Here, we show that Akt counteracts the function of WEE1Hu. Inactivation of Akt by chemotherapeutic drugs or the phosphatidylinositide-3-OH kinase inhibitor LY294002 induced G2/M arrest together with the inhibitory phosphorylation of Cdc2. Because the increased Cdc2 phosphorylation was completely suppressed by wee1hu gene silencing, WEE1Hu was associated with G2/M arrest induced by Akt inactivation. Further analyses revealed that Akt directly bound to and phosphorylated WEE1Hu during the S to G2 phase. Serine-642 was identified as an Akt-dependent phosphorylation site. WEE1Hu kinase activity was not affected by serine-642 phosphorylation. We revealed that serine-642 phosphorylation promoted cytoplasmic localization of WEE1Hu. The nuclear-to-cytoplasmic translocation was mediated by phosphorylation-dependent WEE1Hu binding to 14-3-3θ but not 14-3-3β or -σ. These results indicate that Akt promotes G2/M cell cycle progression by inducing phosphorylation-dependent 14-3-3θ binding and cytoplasmic localization of WEE1Hu.

Function and regulation of RhoE

2005 ◽  
Vol 33 (4) ◽  
pp. 649-651 ◽  
Author(s):  
K. Riento ◽  
P. Villalonga ◽  
R. Garg ◽  
A. Ridley
Keyword(s):  
Cell Cycle Progression ◽  
Small Gtpases ◽  
Serine Threonine Kinase ◽  
Cycle Progression ◽  
Cultured Fibroblasts ◽  
Multifunctional Protein ◽  
Threonine Kinase ◽  
Inhibit Cell Cycle Progression ◽  
Rho Family ◽  
Stress Fibre Formation

The three Rnd proteins, Rnd1, Rnd2 and RhoE/Rnd3, are a subset of Rho family proteins that are unusual in that they bind but do not hydrolyse GTP, and are therefore not regulated by the classical GTP/GDP conformational switch of small GTPases. Increased expression of each Rnd protein induces loss of stress fibres in cultured fibroblasts and epithelial cells, acting antagonistically to RhoA, which stimulates stress fibre formation. RhoE is farnesylated and localizes partly on membranes, including the Golgi and plasma membrane, and in the cytosol. RhoE inhibits RhoA signalling in part by binding to the RhoA-activated serine/threonine kinase ROCK I (Rho-associated kinase I), thereby preventing it from phosphorylating its targets. RhoE activity is itself regulated by phosphorylation by ROCK I on multiple sites. RhoE phosphorylation enhances its stability, leading to an increase in RhoE levels. In addition, phosphorylation reduces its association with membranes and correlates with its ability to induce loss of stress fibres. RhoE also acts independently of ROCK to inhibit cell cycle progression, in part by preventing translation of cyclin D1, and to inhibit transformation of fibroblasts by oncogenic H-Ras. RhoE is therefore a multifunctional protein whose localization and actions are regulated by phosphorylation.

scholarly journals The membrane-associated form of cyclin D1 enhances cellular invasion

Oncogenesis ◽  
2020 ◽  
Vol 9 (9) ◽  
Author(s):  
Ke Chen ◽  
Xuanmao Jiao ◽  
Anthony Ashton ◽  
Agnese Di Rocco ◽  
Timothy G. Pestell ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cyclin D1 ◽  
Cell Cycle Progression ◽  
Cellular Proliferation ◽  
Cytoplasmic Membrane ◽  
Cellular Migration ◽  
Serine Threonine Kinase ◽  
Cycle Progression ◽  
17Β Estradiol ◽  
Localized Form

Abstract The essential G1-cyclin, CCND1, is a collaborative nuclear oncogene that is frequently overexpressed in cancer. D-type cyclins bind and activate CDK4 and CDK6 thereby contributing to G1–S cell-cycle progression. In addition to the nucleus, herein cyclin D1 was also located in the cytoplasmic membrane. In contrast with the nuclear-localized form of cyclin D1 (cyclin D1NL), the cytoplasmic membrane-localized form of cyclin D1 (cyclin D1MEM) induced transwell migration and the velocity of cellular migration. The cyclin D1MEM was sufficient to induce G1–S cell-cycle progression, cellular proliferation, and colony formation. The cyclin D1MEM was sufficient to induce phosphorylation of the serine threonine kinase Akt (Ser473) and augmented extranuclear localized 17β-estradiol dendrimer conjugate (EDC)-mediated phosphorylation of Akt (Ser473). These studies suggest distinct subcellular compartments of cell cycle proteins may convey distinct functions.

scholarly journals DNA Aptamers against Vaccinia-Related Kinase (VRK) 1 Block Proliferation in MCF7 Breast Cancer Cells

2021 ◽  
Vol 14 (5) ◽  
pp. 473
Author(s):  
Rebeca Carrión-Marchante ◽  
Valerio Frezza ◽  
Ana Salgado-Figueroa ◽  
M. Isabel Pérez-Morgado ◽  
M. Elena Martín ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
In Vitro Selection ◽  
Dna Aptamers ◽  
Cycle Progression ◽  
Threonine Kinase ◽  
G1 Phase Arrest ◽  
Cancer Types ◽  
Induced Apoptosis

Vaccinia-related kinase (VRK) 1 is a serin/threonine kinase that plays an important role in DNA damage response (DDR), phosphorylating some proteins involved in this process such as 53BP1, NBS1 or H2AX, and in the cell cycle progression. In addition, VRK1 is overexpressed in many cancer types and its correlation with poor prognosis has been determined, showing VRK1 as a new therapeutic target in oncology. Using in vitro selection, high-affinity DNA aptamers to VRK1 were selected from a library of ssDNA. Selection was monitored using the enzyme-linked oligonucleotide assay (ELONA), and the selected aptamer population was cloned and sequenced. Three aptamers were selected and characterized. These aptamers recognized the protein kinase VRK1 with an affinity in the nanomolar range and showed a high sensibility. Moreover, the treatment of the MCF7 breast cell line with these aptamers resulted in a decrease in cyclin D1 levels, and an inhibition of cell cycle progression by G1 phase arrest, which induced apoptosis in cells. These results suggest that these aptamers are specific inhibitors of VRK1 that might be developed as potential drugs for the treatment of cancer.

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