20 results on '"Tsygankova, Oxana"'
Search Results
2. Role of cAMP, PKA and Rap1A in thyroid follicular cell survival
- Author
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Saavedra, Arturo P, Tsygankova, Oxana M, Prendergast, Gregory V, Dworet, Jessica H, Cheng, Guanjun, and Meinkoth, Judy L
- Published
- 2002
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3. Cyclic AMP activates Ras
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Tsygankova, Oxana M, Kupperman, Erik, Wen, Wei, and Meinkoth, Judy L
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- 2000
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4. Rap1GAP impairs cell-matrix adhesion in the absence of effects on cell-cell adhesion
- Author
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Vuchak, Lisa A., Tsygankova, Oxana M., and Meinkoth, Judy L.
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- 2011
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5. Loss of Rap1GAP in Papillary Thyroid Cancer
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Nellore, Anoma, Paziana, Karolina, Ma, Changqing, Tsygankova, Oxana M., Wang, Yan, Puttaswamy, Kanchan, Iqbal, Ammarah U., Franks, Susanna R., Lv, Yu, Troxel, Andrea B., Feldman, Michael D., Meinkoth, Judy L., and Brose, Marcia S.
- Published
- 2009
6. Differential translocation of protein kinase C isozymes by phorbol esters, EGF, and ANG II in rat liver WB cells
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Maloney, Judith A., Tsygankova, Oxana, Szot, Agnieszka, Yang, Lijun, Li, Quiyang, and Williamson, John R.
- Subjects
Cell compartmentation -- Research ,Protein kinases -- Physiological aspects ,Phorbol esters -- Physiological aspects ,Epidermal growth factor -- Physiological aspects ,Angiotensin -- Physiological aspects ,Liver cells -- Physiological aspects ,Biological sciences - Abstract
The effects of phorbol esters, epidermal growth factor (EGF) and angiotensin (ANG) II on the translocation of the alpha, delta and epsilon isozymes of protein kinase C in rat liver epithelial cells were investigated through Western blot analysis following subcellular fractionation of treated tissues. Phorbol esters induced the highest degree of membrane translocation of the different isozymes. Although the magnitude of translocation induced by both EGF and ANG II is low, the significant translocation of the delta and epsilon isozymes is enough to explain spatially defined effects.
- Published
- 1998
7. A unique role for clathrin light chain A in cell spreading and migration.
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Tsygankova, Oxana M. and Keen, James H.
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CELL migration , *FOCAL adhesions , *CLATHRIN , *INTEGRINS , *STRUCTURAL components , *CELL membranes - Abstract
Clathrin heavy chain is the structural component of the clathrin triskelion, but unique functions for the two distinct and highly conserved clathrin light chains (CLCa and CLCb, also known as CLTA and CLTB, respectively) have been elusive. Here, we show that following detachment and replating, CLCa is uniquely responsible for promoting efficient cell spreading and migration. Selective depletion of CLCa, but not of CLCb, reduced the initial phase of isotropic spreading of HeLa, H1299 and HEK293 cells by 60-80% compared to siRNA controls, and wound closure and motility by ~50%. Surface levels of ß1-integrins were unaffected by CLCa depletion. However, CLCa was required for effective targeting of FAK (also known as PTK2) and paxillin to the adherent surface of spreading cells, for integrin-mediated activation of Src, FAK and paxillin, and for maturation of focal adhesions, but not their microtubule-based turnover. Depletion of CLCa also blocked the interaction of clathrin with the nucleation-promoting factor WAVE complex, and altered actin distribution. Furthermore, preferential recruitment of CLCa to budding protrusions was also observed. These results comprise the first identification of CLCa-specific functions, with implications for normal and neoplastic integrin-based signaling and cell migration. [ABSTRACT FROM AUTHOR]
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- 2019
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8. EFFECT OF MOBILE APPLICATIONS FOR PHYSICAL ACTIVITY TRACKING ON EXERCISE TOLERANCE IN PATIENTS WITH HYPERTENSION AND CORONARY ARTERY DISEASE.
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Tsygankova, Oxana, Ponkin, Serghei, and Veretyuk, Varvara
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- 2022
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9. Activation of ERK by Ca2+ store depletion in rat liver epithelial cells
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Maloney, Judith A., Tsygankova, Oxana M., Yang, Lijun, Li, Quiyang, Szot, Agnieszka, Baysal, Kemal, and Williamson, John R.
- Subjects
Rats -- Physiological aspects ,Liver -- Physiological aspects ,Epithelial cells -- Physiological aspects ,Protein kinases -- Physiological aspects ,Calcium in the body -- Research ,Biological sciences - Abstract
The relationship between the extracellular signal-regulated protein kinase (ERK) and Ca2+ pool in rat liver epithelial cells was investigated. Results showed that ERK activity is increased by Ca2+ pool depletion induced by two independent methods. The first method involved the Ca2+ pool depletion by thapsigarin, while the second involved the addition of extracellular EGTA. Moreover, the increase in ERK activity by Ca2+ pool depletion was via the tyrosine kinase pathway.
- Published
- 1999
10. Thyroid-stimulating Hormone/cAMP and Glycogen Synthase Kinase 3β Elicit Opposing Effects on Rap1GAP Stability.
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Tsygankova, Oxana M., Feshchenko, Elena, Klein, Peter S., and Meinkoth, Judy L.
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GTPASE-activating protein , *HORMONES , *CYCLIC adenylic acid , *PROTEINS , *UBIQUITIN , *THYROID gland , *GLYCOGEN - Abstract
Beyond regulating Rap activity, little is known regarding the regulation and function of the Rap GTPase-activating protein Rap1GAP. Tuberin and E6TP1 protein levels are tightly regulated through ubiquitin-mediated proteolysis. A role for these RapGAPs, along with SPA-1, as tumor suppressors has been demonstrated. Whether RaplGAP performs a similar role was investigated. We now report that Rap1GAP protein levels are dynamically regulated in thyroid-stimulating hormone (TSH)-dependent thyroid cells. Upon TSH withdrawal, Rap1GAP undergoes a net increase in phosphorylation followed by proteasome-mediated degradation. Sequence analysis identified two putative destruction boxes in the Rap1GAP C-terminal domain. Glycogen synthase kinase 3β (GSK3β) phosphorylated Rap1GAP immunoprecipitated from thyroid cells, and GSK3β inhibitors prevented phosphorylation and degradation of endogenous Rap1GAP. Co-expression of GSK3β and Rap1GAP in human embryonic kidney 293 cells stimulated proteasome-dependent Rap1GAP turnover. Mutational analysis established a role for serine 525 in the regulation of Rap1GAP stability. Overexpression of Rap1GAP in thyroid cells impaired TSH/cAMPstimulated p70S6 kinase activity and cell proliferation. These data are the first to show that Rap1GAP protein levels are tightly regulated and are the first to support a role for Rap1GAP as a tumor suppressor. [ABSTRACT FROM AUTHOR]
- Published
- 2004
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11. Activation of ERK by Ca...store depletion in rat liver epithelial cells.
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Maloney, Judith A. and Tsygankova, Oxana M.
- Subjects
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PROTEIN kinases , *PHYSIOLOGICAL effects of calcium - Abstract
Presents a study that determined if extracellular signal-regulated protein kinase can be activated through depletion of stored calcium in the epithelial cells of liver rat. Mechanism of calcium release from epithelial cells; Methodology; Results; Discussion.
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- 1999
12. Angiotensin II induces diverse signal transduction pathways via both G.
- Author
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Tsygankova, Oxana M., Peng, Ming, Maloney, Judith A., Hopkins, Nancy, and Williamson, John R.
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- 1998
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13. Downregulation of Rap1GAP in Human Tumor Cells Alters Cell/Matrix and Cell/Cell Adhesion.
- Author
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Tsygankova, Oxana M., Ma, Changqing, Tang, Waixing, Korch, Christopher, Feldman, Michael D., Yu Lv, Brose, Marcia S., and Meinkoth, Judy L.
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CANCER cells , *GENE expression , *CELL communication , *CYTOLOGY ,TUMOR genetics - Abstract
Rap1GAP expression is decreased in human tumors. The significance of its downregulation is unknown. We show that Rap1GAP expression is decreased in primary colorectal carcinomas. To elucidate the advantages conferred on tumor cells by loss of Rap1GAP, Rap1GAP expression was silenced in human colon carcinoma cells. Suppressing Rap1GAP induced profound alterations in cell adhesion. Rap1GAP-depleted cells exhibited defects in cell/cell adhesion that included an aberrant distribution of adherens junction proteins. Depletion of Rap1GAP enhanced adhesion and spreading on collagen. Silencing of Rap expression normalized spreading and restored E-cadherin, ß-catenin, and p120-catenin to cell/cell contacts, indicating that unrestrained Rap activity underlies the alterations in cell adhesion. The defects in adherens junction protein distribution required integrin signaling as E-cadherin and p120-catenin were restored at cell/cell contacts when cells were plated on poly-L-lysine. Unexpectedly, Src activity was increased in Rap1GAP-depleted cells. Inhibition of Src impaired spreading and restored E-cadherin at cell/cell contacts. These findings provide the first evidence that Rap1GAP contributes to cell/cell adhesion and highlight a role for Rap1GAP in regulating cell/matrix and cell/cell adhesion. The frequent downregulation of Rap1GAP in epithelial tumors where alterations in cell/cell and cell/matrix adhesion are early steps in tumor dissemination supports a role for Rap1GAP depletion in tumor progression [ABSTRACT FROM AUTHOR]
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- 2010
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14. Downregulation of Rap1GAP Contributes to Ras Transformation.
- Author
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Tsygankova, Oxana M., Prendergast, Gregory V., Puttaswamy, Kanchan, Yan Wang, Feldman, Michael D., Hongbin Wang, Brose, Marcia S., and Meinkoth, Judy L.
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GENE expression , *THYROID gland tumors , *CELL lines , *CELL migration , *ONCOGENES , *LABORATORY rats - Abstract
Although abundant in well-differentiated rat thyroid cells, Rap1GAP expression was extinguished in a subset of human thyroid tumor-derived cell lines. Intriguingly, Rap1GAP was downregulated selectively in tumor cell lines that had acquired a mesenchymal morphology. Restoring Rap1GAP expression to these cells inhibited cell migration and invasion, effects that were correlated with the inhibition of Rap1 and Rac1 activity. The reexpression of Rap1GAP also inhibited DNA synthesis and anchorage-independent proliferation. Conversely, eliminating Rap1GAP expression in rat thyroid cells induced a transient increase in cell number. Strikingly, Rap1GAP expression was abolished by Ras transformation. The downregulation of Rap1GAP by Ras required the activation of the Raf/MEK/extracellular signal-regulated kinase cascade and was correlated with the induction of mesenchymal morphology and migratory behavior. Remarkably, the acute expression of oncogenic Ras was sufficient to downregulate Rap1GAP expression in rat thyroid cells, identifying Rap1GAP as a novel target of oncogenic Ras. Collectively, these data implicate Rap1GAP as a putative tumor/invasion suppressor in the thyroid. In support of that notion, Rap1GAP was highly expressed in normal human thyroid cells and downregulated in primary thyroid tumors. [ABSTRACT FROM AUTHOR]
- Published
- 2007
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15. TULA proteins bind to ABCE-1, a host factor of HIV-1 assembly, and inhibit HIV-1 biogenesis in a UBA-dependent fashion
- Author
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Smirnova, Evgeniya V., Collingwood, Therese S., Bisbal, Catherine, Tsygankova, Oxana M., Bogush, Marina, Meinkoth, Judy L., Henderson, Earl E., Annan, Roland S., and Tsygankov, Alexander Y.
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GREEN fluorescent protein , *FLUORESCENT polymers , *PROTEINS , *MASS spectrometry - Abstract
Abstract: TULA, a recently identified UBA- and SH3-containing protein, has previously been shown to regulate cell signaling through protein tyrosine kinases. In order to search for novel functions of TULA, we identified, using mass spectrometry, proteins associated with TULA. ABCE-1 also known as RLI and HP68, a host factor of HIV-1 assembly, was found among TULA-associated proteins in these experiments. Considering an important role of ABCE-1 in HIV-1 assembly, we were compelled to analyze the effect of TULA on HIV-1 biogenesis. Our study provides evidence that TULA proteins substantially inhibit production of both sub-genomic and full-length HIV-1 viral particles and that the effect of TULA is dependent on UBA domain-mediated interactions. The primary role of ABCE-1 in the effect of TULA appears to be the recruitment of TULA to the sites of HIV-1 assembly where TULA interferes with the late steps of the HIV-1 life cycle, most likely by disrupting essential ubiquitylation-dependent events that remain to be identified. [Copyright &y& Elsevier]
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- 2008
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16. Ras Triggers Ataxia-telangiectasia-mutated and Rad-3-related Activation and Apoptosis through Sustained Mitogenic Signaling.
- Author
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Fikaris, Aphrothiti J., Lewis, Aurélia E., Abulaiti, Adili, Tsygankova, Oxana M., and Meinkoth, Judy L.
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RAS oncogenes , *THYROID diseases , *APOPTOSIS , *CELL cycle , *DNA damage , *BIOCHEMISTRY - Abstract
Genetic evidence indicates that Ras plays a critical role in the initiation and progression of human thyroid tumors. Paradoxically, acute expression of activated Ras in normal rat thyroid cells induced deregulated cell cycle progression and apoptosis. We investigated whether cell cycle progression was required for Ras-stimulated apoptosis. Ras increased CDK-2 activity following its introduction into quiescent cells. Apoptotic cells exhibited a sustained increase in CDK-2 activity, accompanied by the loss of CDK-2-associated p27. Blockade of Ras-induced CDK-2 activity and S phase entry via overexpression of p27 inhibited apoptosis. Inactivation of the retinoblastoma protein in quiescent cells through expression of HPV-E7 stimulated cell cycle progression and apoptosis, indicating that deregulated cell cycle progression is sufficient to induce apoptosis. Ras failed to induce G1 phase growth arrest in normal rat thyroid cells. Rather, Ras-expressing thyroid cells progressed into S and G2 phases and evoked a checkpoint response characterized by the activation of ATR. Ras-stimulated ATR activity, as evidenced by Chk1 and p53 phosphorylation, was blocked by p27, suggesting that cell cycle progression triggers checkpoint activation, likely as a consequence of replication stress. These data reveal that Ras is capable of inducing a DNA damage response with characteristics similar to those reported in precancerous lesions. Our findings also suggest that the frequent mutational activation of Ras in thyroid tumors reflects the ability of Ras-expressing cells to bypass checkpoints and evade apoptosis rather than to simply increase proliferative potential. [ABSTRACT FROM AUTHOR]
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- 2006
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17. Protein kinase A and B-Raf mediate extracellular signal-regulated kinase activation by thyrotropin.
- Author
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Vuchak LA, Tsygankova OM, Prendergast GV, and Meinkoth JL
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- Animals, Cell Line, Cyclic AMP physiology, DNA Replication physiology, Enzyme Activation physiology, Rats, Rats, Wistar, Cyclic AMP-Dependent Protein Kinases physiology, Extracellular Signal-Regulated MAP Kinases metabolism, MAP Kinase Signaling System physiology, Proto-Oncogene Proteins B-raf physiology, Thyrotropin physiology
- Abstract
Thyrotropin (TSH) regulates thyroid cell proliferation and function through cAMP-mediated signaling pathways that activate protein kinase A (PKA) and Epac/Rap1. The respective roles of PKA versus Epac/Rap1 in TSH signaling remain unclear. We set out to determine whether PKA and/or Rap1 mediate extracellular signal-regulated kinase (ERK) activation by TSH. Neither blocking Rap1 activity nor silencing the expression of Rap1 impaired TSH or forskolin-induced ERK activation in Wistar rat thyroid cells. Direct activation of Epac1 failed to stimulate ERK activity in starved cells, suggesting that Epac-induced Rap1 activity is not coupled to ERK activation in rat thyroid cells. By contrast, PKA activity was required for cAMP-stimulated ERK phosphorylation and was sufficient to increase ERK phosphorylation in starved cells. Expression of dominant-negative Ras inhibited ERK activation by TSH, forskolin, and N(6)-monobutyryl (6MB)-cAMP, a selective activator of PKA. Silencing the expression of B-Raf also inhibited ERK activation by TSH, forskolin, and 6MB-cAMP, but not that stimulated by insulin or serum. Depletion of B-Raf impaired TSH-induced DNA synthesis, indicating a functional role for B-Raf in TSH-regulated proliferation. Collectively, these results position PKA, Ras, and B-Raf as upstream regulators of ERK activation and identify B-Raf as a selective target of cAMP-elevating agents in thyroid cells. These data provide the first evidence for a functional role for B-Raf in TSH signaling.
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- 2009
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18. Ras induces chromosome instability and abrogation of the DNA damage response.
- Author
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Abulaiti A, Fikaris AJ, Tsygankova OM, and Meinkoth JL
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- Animals, Apoptosis, Ataxia Telangiectasia Mutated Proteins, Cell Cycle, Cell Cycle Proteins metabolism, DNA Repair, Histones metabolism, Protein Serine-Threonine Kinases metabolism, Rats, Rats, Wistar, Thyroid Neoplasms genetics, Cell Transformation, Neoplastic, Chromosomal Instability, DNA Damage, Genes, ras physiology
- Abstract
Ras mutations are frequent in thyroid tumors, the most common endocrine malignancy. The ability of Ras to transform thyroid cells is thought to rely on its mitogenic activity. Unexpectedly, acute expression of activated Ras in normal rat thyroid cells induced a DNA damage response, followed by apoptosis. Notably, a subpopulation of cells evaded apoptosis and emerged with features of transformation, including the loss of epithelial morphology, dedifferentiation, and the acquisition of hormone- and anchorage-independent proliferation. Strikingly, the surviving cells showed marked chromosomal instability. Acutely, Ras stimulated replication stress as evidenced by the induction of ataxia telangiectasia mutated and Rad3-related protein kinase (ATR) activity (Chk1 phosphorylation) and of gammaH2A.X, a marker of DNA damage. Despite the activation of a checkpoint, cells continued through mitosis in the face of DNA damage, resulting in an increase in cells harboring micronuclei, an indication of defects in chromosome segregation and other forms of chromosome damage. Cells that survived exposure to Ras continued to exhibit replication stress (ATR activation) but no longer exhibited gammaH2A.X or full activation of p53. When rechallenged with Ras or DNA-damaging agents, the surviving cells were more resistant to apoptosis than parental cells. These data show that acute expression of activated Ras is sufficient to induce chromosomal instability in the absence of other signals, and suggest that Ras-induced chromosomal instability arises as a consequence of defects in the processing of DNA damage. Hence, abrogation of the DNA damage response may constitute a novel mechanism for Ras transformation.
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- 2006
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19. Histone deacetylase is a target of valproic acid-mediated cellular differentiation.
- Author
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Gurvich N, Tsygankova OM, Meinkoth JL, and Klein PS
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- Cell Differentiation drug effects, Cell Differentiation physiology, Cyclin-Dependent Kinase Inhibitor p21, Cyclins physiology, Enzyme Activation drug effects, Humans, Isoenzymes antagonists & inhibitors, K562 Cells, Mitogen-Activated Protein Kinases metabolism, U937 Cells, Enzyme Inhibitors pharmacology, Histone Deacetylase Inhibitors, Valproic Acid analogs & derivatives, Valproic Acid pharmacology
- Abstract
Valproic acid (VPA), a well-established therapy for seizures and bipolar disorder, has recently been shown to inhibit histone deacetylases (HDACs). Similar to more widely studied HDAC inhibitors, VPA can cause growth arrest and induce differentiation of transformed cells in culture. Whether this effect of VPA is through inhibition of HDACs or modulation of another target of VPA has not been tested. We have used a series of VPA analogs to establish a pharmacological profile for HDAC inhibition. We find that VPA and its analogs inhibit multiple HDACs from class I and class II (but not HDAC6 or HDAC10) with a characteristic order of potency in vitro. These analogs also induce hyperacetylation of core histones H3 and H4 in intact cells with an order of potency that parallels in vitro inhibition. VPA and VPA analogs induce differentiation in hematopoietic cell lines in a p21-dependent manner, and the order of potency for induction of differentiation parallels the potencies for inhibition in vitro, as well as for acetylation of histones associated with the p21 promoter, supporting the argument that differentiation caused by VPA is mediated through inhibition of HDACs. These findings provide additional evidence that VPA, a well-tolerated, orally administered drug with extensive clinical experience, may serve as an effective chemotherapeutic agent through targeting of HDACs.
- Published
- 2004
- Full Text
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20. Differential signaling of cyclic AMP: opposing effects of exchange protein directly activated by cyclic AMP and cAMP-dependent protein kinase on protein kinase B activation.
- Author
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Mei FC, Qiao J, Tsygankova OM, Meinkoth JL, Quilliam LA, and Cheng X
- Subjects
- Base Sequence, Cell Line, Colforsin pharmacology, DNA Primers, Enzyme Activation, Humans, Phosphatidylinositol 3-Kinases metabolism, Phosphorylation, Proto-Oncogene Proteins c-akt, Transfection, rap1 GTP-Binding Proteins metabolism, Cyclic AMP metabolism, Cyclic AMP-Dependent Protein Kinases metabolism, Guanine Nucleotide Exchange Factors metabolism, Protein Serine-Threonine Kinases, Proto-Oncogene Proteins metabolism, Signal Transduction
- Abstract
The recent discovery of Epac, a novel cAMP receptor protein, opens up a new dimension in studying cAMP-mediated cell signaling. It is conceivable that many of the cAMP functions previously attributed to cAMP-dependent protein kinase (PKA) are in fact also Epac-dependent. The finding of an additional intracellular cAMP receptor provides an opportunity to further dissect the divergent roles that cAMP exerts in different cell types. In this study, we probed cross-talk between cAMP signaling and the phosphatidylinositol 3-kinase/PKB pathways. Specifically, we examined the modulatory effects of cAMP on PKB activity by monitoring the specific roles that Epac and PKA play individually in regulating PKB activity. Our study suggests a complex regulatory scheme in which Epac and PKA mediate the opposing effects of cAMP on PKB regulation. Activation of Epac leads to a phosphatidylinositol 3-kinase-dependent PKB activation, while stimulation of PKA inhibits PKB activity. Furthermore, activation of PKB by Epac requires the proper subcellular targeting of Epac. The opposing effects of Epac and PKA on PKB activation provide a potential mechanism for the cell type-specific differential effects of cAMP. It is proposed that the net outcome of cAMP signaling is dependent upon the dynamic abundance and distribution of intracellular Epac and PKA.
- Published
- 2002
- Full Text
- View/download PDF
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