LIVIVO - Search results -

Search results

Result 1 - 10 of total 18

Search options

Article ; Online: Wnt signaling pathways meet Rho GTPases.

Schlessinger, Karni / Hall, Alan / Tolwinski, Nicholas

2009 Volume 23, Issue 3, Page(s) 265–277

Abstract: Wnt ligands and their receptors orchestrate many essential cellular and physiological processes. During development they control differentiation, proliferation, migration, and patterning, while in the adult, they regulate tissue homeostasis, primarily ... ...

Abstract	Wnt ligands and their receptors orchestrate many essential cellular and physiological processes. During development they control differentiation, proliferation, migration, and patterning, while in the adult, they regulate tissue homeostasis, primarily through their effects on stem cell proliferation and differentiation. Underpinning these diverse biological activities is a complex set of intracellular signaling pathways that are still poorly understood. Rho GTPases have emerged as key mediators of Wnt signals, most notably in the noncanonical pathways that involve polarized cell shape changes and migrations, but also more recently in the canonical pathway leading to beta-catenin-dependent transcription. It appears that Rho GTPases integrate Wnt-induced signals spatially and temporally to promote morphological and transcriptional changes affecting cell behavior.
MeSH term(s)	Animals ; Cell Division ; Cell Movement ; Cell Polarity ; Chickens ; Drosophila ; Humans ; Mammals ; Models, Biological ; Mutation ; Neurons/cytology ; Neurons/metabolism ; Signal Transduction ; Wnt Proteins/genetics ; Wnt Proteins/metabolism ; Xenopus laevis ; Zebrafish ; beta Catenin/metabolism ; rho GTP-Binding Proteins/genetics ; rho GTP-Binding Proteins/metabolism
Chemical Substances	Wnt Proteins ; beta Catenin ; rho GTP-Binding Proteins (EC 3.6.5.2)
Language	English
Publishing date	2009-02-01
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	806684-x
ISSN	1549-5477 ; 0890-9369
ISSN (online)	1549-5477
ISSN	0890-9369
DOI	10.1101/gad.1760809
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 2292: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 54: Show issues

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾
- See ZB MED holdings
- Order with fees

Article: Malignant transformation but not normal cell growth depends on signal transducer and activator of transcription 3.

Schlessinger, Karni / Levy, David E

Cancer research

2005 Volume 65, Issue 13, Page(s) 5828–5834

Abstract: Signal transducer and activator of transcription 3 (STAT3) has been indirectly implicated in numerous fundamental cellular processes, including proliferation, survival, and differentiation. We provide genetic evidence from studies of STAT3-null cells ... ...

Abstract	Signal transducer and activator of transcription 3 (STAT3) has been indirectly implicated in numerous fundamental cellular processes, including proliferation, survival, and differentiation. We provide genetic evidence from studies of STAT3-null cells that STAT3 is dispensable for normal growth of mouse fibroblasts in culture. STAT3 contributed to the full induction of some (typified by c-fos) but not all (typified by c-myc) immediate early gene expression, but STAT3-independent processes were sufficient to support full cell growth and survival. However, STAT3 was required to manifest a transformed state following expression of v-src, and STAT3-null cells were impaired for anchorage-independent growth as colonies in soft agar and as tumors in mice. The data suggest that STAT3 mediates the maintenance of focal adhesion kinase activity in the absence of cell adhesion by suppressing the action of an inhibitory phosphatase.
MeSH term(s)	Animals ; Cell Adhesion/genetics ; Cell Growth Processes/physiology ; Cell Transformation, Neoplastic/genetics ; Cell Transformation, Neoplastic/metabolism ; Cell Transformation, Neoplastic/pathology ; Cells, Cultured ; DNA-Binding Proteins/deficiency ; DNA-Binding Proteins/genetics ; Enzyme Activation ; Fibroblasts/physiology ; Focal Adhesion Kinase 1 ; Focal Adhesion Protein-Tyrosine Kinases ; Gene Expression Regulation ; Genes, fos ; Genes, src ; Mice ; Mice, Inbred BALB C ; Oncogene Protein pp60(v-src)/biosynthesis ; Oncogene Protein pp60(v-src)/genetics ; Protein-Tyrosine Kinases/metabolism ; Proto-Oncogene Proteins c-fos/biosynthesis ; Proto-Oncogene Proteins c-fos/genetics ; STAT3 Transcription Factor ; Trans-Activators/deficiency ; Trans-Activators/genetics
Chemical Substances	DNA-Binding Proteins ; Proto-Oncogene Proteins c-fos ; STAT3 Transcription Factor ; Stat3 protein, mouse ; Trans-Activators ; Protein-Tyrosine Kinases (EC 2.7.10.1) ; Focal Adhesion Kinase 1 (EC 2.7.10.2) ; Focal Adhesion Protein-Tyrosine Kinases (EC 2.7.10.2) ; Oncogene Protein pp60(v-src) (EC 2.7.10.2) ; Ptk2 protein, mouse (EC 2.7.10.2)
Language	English
Publishing date	2005-07-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	1432-1
ISSN	1538-7445 ; 0008-5472
ISSN (online)	1538-7445
ISSN	0008-5472
DOI	10.1158/0008-5472.CAN-05-0317
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Full text

In stock of ZB MED Cologne/Königswinter

Uh III Zs.135/5: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article: GSK-3beta sets Snail's pace.

Schlessinger, Karni / Hall, Alan

Nature cell biology

2004 Volume 6, Issue 10, Page(s) 913–915

MeSH term(s)	Amino Acid Sequence ; Cadherins/metabolism ; Cell Line, Tumor ; Consensus Sequence ; DNA-Binding Proteins/chemistry ; DNA-Binding Proteins/drug effects ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Enzyme Inhibitors ; Epithelial Cells/cytology ; Epithelial Cells/metabolism ; Gene Expression Regulation, Neoplastic ; Glycogen Synthase Kinase 3/drug effects ; Glycogen Synthase Kinase 3/metabolism ; Glycogen Synthase Kinase 3 beta ; Humans ; Leupeptins/pharmacology ; Mesoderm/cytology ; Mesoderm/metabolism ; Mutation ; Phosphorylation ; Serine/chemistry ; Signal Transduction ; Snail Family Transcription Factors ; Substrate Specificity ; Transcription Factors/chemistry ; Transcription Factors/drug effects ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Zinc Fingers
Chemical Substances	Cadherins ; DNA-Binding Proteins ; Enzyme Inhibitors ; Leupeptins ; Snail Family Transcription Factors ; Transcription Factors ; Serine (452VLY9402) ; GSK3B protein, human (EC 2.7.11.1) ; Glycogen Synthase Kinase 3 beta (EC 2.7.11.1) ; Glycogen Synthase Kinase 3 (EC 2.7.11.26) ; benzyloxycarbonylleucyl-leucyl-leucine aldehyde (RF1P63GW3K)
Language	English
Publishing date	2004-10
Publishing country	England
Document type	News ; Comment
ZDB-ID	1474722-4
ISSN	1476-4679 ; 1465-7392
ISSN (online)	1476-4679
ISSN	1465-7392
DOI	10.1038/ncb1004-913
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 5169: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 12: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: APC nuclear membrane association and microtubule polarity.

Collin, Ludovic / Schlessinger, Karni / Hall, Alan

Biology of the cell

2008 Volume 100, Issue 4, Page(s) 243–252

Abstract: Background information: Directional cell migration is a fundamental feature of embryonic development, the inflammatory response and the metastatic spread of cancer. Migrating cells have a polarized morphology with an asymmetric distribution of ... ...

Abstract	Background information: Directional cell migration is a fundamental feature of embryonic development, the inflammatory response and the metastatic spread of cancer. Migrating cells have a polarized morphology with an asymmetric distribution of signalling molecules and of the actin and microtubule cytoskeletons. The dynamic reorganization of the actin cytoskeleton provides the major driving force for migration in all mammalian cell types, but microtubules also play an important role in many cells, most notably neuronal precursors. Results: We previously showed, using primary fibroblasts and astrocytes in in vitro scratch-induced migration assays, that the accumulation of APC (adenomatous polyposis coli; the APC tumour suppressor protein) at microtubule plus-ends promotes their association with the plasma membrane at the leading edge. This is required for polarization of the microtubule cytoskeleton during directional migration. Here, we have examined the organization of microtubules in the soma of migrating neurons and fibroblasts. Conclusions: We find that APC, through a direct interaction with the NPC (nuclear pore complex) protein Nup153 (nucleoporin 153), promotes the association of microtubules with the nuclear membrane.
MeSH term(s)	Adenomatous Polyposis Coli ; Adenomatous Polyposis Coli Protein/analysis ; Adenomatous Polyposis Coli Protein/metabolism ; Animals ; Astrocytes/cytology ; Cell Culture Techniques ; Cell Movement ; Cell Polarity ; Centrosome/metabolism ; Fibroblasts/cytology ; HeLa Cells ; Humans ; Microscopy, Confocal ; Microtubules/metabolism ; Neurons/cytology ; Neurons/metabolism ; Nuclear Envelope/metabolism ; Nuclear Pore/metabolism ; Nuclear Pore Complex Proteins/genetics ; Nuclear Pore Complex Proteins/metabolism ; Rats ; Sequence Deletion
Chemical Substances	Adenomatous Polyposis Coli Protein ; NUP153 protein, human ; Nuclear Pore Complex Proteins
Language	English
Publishing date	2008-04
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	245745-3
ISSN	1768-322X ; 0399-0311 ; 0248-4900
ISSN (online)	1768-322X
ISSN	0399-0311 ; 0248-4900
DOI	10.1042/BC20070123
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 758: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Cdc42 and noncanonical Wnt signal transduction pathways cooperate to promote cell polarity.

Schlessinger, Karni / McManus, Edward J / Hall, Alan

The Journal of cell biology

2007 Volume 178, Issue 3, Page(s) 355–361

Abstract: Scratch-induced disruption of cultured monolayers induces polarity in front row cells that can be visualized by spatially localized polymerization of actin at the front of the cell and reorientation of the centrosome/Golgi to face the leading edge. We ... ...

Abstract	Scratch-induced disruption of cultured monolayers induces polarity in front row cells that can be visualized by spatially localized polymerization of actin at the front of the cell and reorientation of the centrosome/Golgi to face the leading edge. We previously reported that centrosomal reorientation and microtubule polarization depend on a Cdc42-regulated signal transduction pathway involving activation of the Par6/aPKC complex followed by inhibition of GSK-3beta and accumulation of the adenomatous polyposis coli (APC) protein at the plus ends of leading-edge microtubules. Using monolayers of primary rodent embryo fibroblasts, we show here that dishevelled (Dvl) and axin, two major components of the Wnt signaling pathway are required for centrosome reorientation and that Wnt5a is required for activation of this pathway. We conclude that disruption of cell-cell contacts leads to the activation of a noncanonical Wnt/dishevelled signal transduction pathway that cooperates with Cdc42/Par6/aPKC to promote polarized reorganization of the microtubule cytoskeleton.
MeSH term(s)	Adaptor Proteins, Signal Transducing/genetics ; Adaptor Proteins, Signal Transducing/metabolism ; Adenomatous Polyposis Coli Protein/metabolism ; Animals ; Axin Protein ; Cell Communication/physiology ; Cell Polarity ; Cells, Cultured ; Centrosome/metabolism ; Cytoskeleton/metabolism ; Dishevelled Proteins ; Fibroblasts/cytology ; Fibroblasts/metabolism ; Glycogen Synthase Kinase 3/metabolism ; Golgi Apparatus/metabolism ; Mice ; Microtubules/metabolism ; Phosphoproteins/genetics ; Phosphoproteins/metabolism ; Protein Kinase C/metabolism ; RNA, Small Interfering/genetics ; RNA, Small Interfering/metabolism ; Rats ; Repressor Proteins/genetics ; Repressor Proteins/metabolism ; Signal Transduction/physiology ; Wnt Proteins/genetics ; Wnt Proteins/metabolism ; cdc42 GTP-Binding Protein/genetics ; cdc42 GTP-Binding Protein/metabolism
Chemical Substances	Adaptor Proteins, Signal Transducing ; Adenomatous Polyposis Coli Protein ; Axin Protein ; Dishevelled Proteins ; Phosphoproteins ; RNA, Small Interfering ; Repressor Proteins ; Wnt Proteins ; PKC-3 protein (EC 2.7.11.13) ; Protein Kinase C (EC 2.7.11.13) ; Glycogen Synthase Kinase 3 (EC 2.7.11.26) ; cdc42 GTP-Binding Protein (EC 3.6.5.2)
Language	English
Publishing date	2007-07-30
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218154-x
ISSN	1540-8140 ; 0021-9525
ISSN (online)	1540-8140
ISSN	0021-9525
DOI	10.1083/jcb.200701083
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Full text

In stock of ZB MED Cologne/Königswinter

Ub I Zs.190: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article: Cdc42 and noncanonical Wnt signal transduction pathways cooperate to promote cell polarity

Schlessinger, Karni / McManus, Edward J / Hall, Alan

Journal of cell biology. 2007 July 30, v. 178, no. 3

2007

Abstract	Scratch-induced disruption of cultured monolayers induces polarity in front row cells that can be visualized by spatially localized polymerization of actin at the front of the cell and reorientation of the centrosome/Golgi to face the leading edge. We previously reported that centrosomal reorientation and microtubule polarization depend on a Cdc42-regulated signal transduction pathway involving activation of the Par6/aPKC complex followed by inhibition of GSK-3β and accumulation of the adenomatous polyposis coli (APC) protein at the plus ends of leading-edge microtubules. Using monolayers of primary rodent embryo fibroblasts, we show here that dishevelled (Dvl) and axin, two major components of the Wnt signaling pathway are required for centrosome reorientation and that Wnt5a is required for activation of this pathway. We conclude that disruption of cell-cell contacts leads to the activation of a noncanonical Wnt/dishevelled signal transduction pathway that cooperates with Cdc42/Par6/aPKC to promote polarized reorganization of the microtubule cytoskeleton.
Language	English
Dates of publication	2007-0730
Size	p. 355-361.
Publishing place	The Rockefeller University Press
Document type	Article
ZDB-ID	218154-x
ISSN	1540-8140 ; 0021-9525
ISSN (online)	1540-8140
ISSN	0021-9525
Database	NAL-Catalogue (AGRICOLA)

In stock of ZB MED Bonn / Germany

Z 56/32: Show issues

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Characterization of two distinct lymphoproliferative diseases caused by ectopic expression of the Notch ligand DLL4 on T cells.

Xiong, Huizhong / Maraver, Antonio / Latkowski, Jo-Ann / Henderson, Tanya / Schlessinger, Karni / Ding, Yi / Shen, Jie / Tadokoro, Carlos E / Lafaille, Juan J

PloS one

2013 Volume 8, Issue 12, Page(s) e84841

Abstract: Notch signaling is essential for the development of T cell progenitors through the interaction of NOTCH1 receptor on their surface with the ligand, Delta-like 4 (DLL4), which is expressed by the thymic epithelial cells. Notch signaling is quickly shut ... ...

Abstract	Notch signaling is essential for the development of T cell progenitors through the interaction of NOTCH1 receptor on their surface with the ligand, Delta-like 4 (DLL4), which is expressed by the thymic epithelial cells. Notch signaling is quickly shut down once the cells pass β-selection, and CD4/CD8 double positive (DP) cells are unresponsive to Notch. Over the past two decades a number of papers reported that over-activation of Notch signaling causes T cell acute lymphoblastic leukemia (T-ALL), a cancer that prominently features circulating monoclonal CD4/CD8 double positive T cells in different mouse models. However, the possible outcomes of Notch over-activation at different stages of T cell development are unknown, and the fine timing of Notch signaling that results in T-ALL is poorly understood. Here we report, by using a murine model that ectopically expresses DLL4 on developing T cells, that the T-ALL onset is highly dependent on a sustained Notch activity throughout the DP stage, which induces additional mutations to further boost the signaling. In contrast, a shorter period of Notch activation that terminates at the DP stage causes a polyclonal, non-transmissible lymphoproliferative disorder that is also lethal. These observations resolved the discrepancy of previous papers on DLL4 driven hematological diseases in mice, and show the critical importance of the timing and duration of Notch activity.
MeSH term(s)	Adaptor Proteins, Signal Transducing ; Animals ; CD4-Positive T-Lymphocytes/metabolism ; CD4-Positive T-Lymphocytes/pathology ; CD8-Positive T-Lymphocytes/metabolism ; CD8-Positive T-Lymphocytes/pathology ; Calcium-Binding Proteins ; Gene Expression Regulation, Leukemic ; Intracellular Signaling Peptides and Proteins/biosynthesis ; Intracellular Signaling Peptides and Proteins/genetics ; Membrane Proteins/biosynthesis ; Membrane Proteins/genetics ; Mice ; Mice, Transgenic ; Neoplasms, Experimental/genetics ; Neoplasms, Experimental/metabolism ; Neoplasms, Experimental/pathology ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology ; Receptors, Notch/genetics ; Receptors, Notch/metabolism ; Signal Transduction
Chemical Substances	Adaptor Proteins, Signal Transducing ; Calcium-Binding Proteins ; DLL4 protein, mouse ; Intracellular Signaling Peptides and Proteins ; Membrane Proteins ; Receptors, Notch
Language	English
Publishing date	2013-12-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0084841
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Gene expression in WAT from healthy humans and monkeys correlates with FGF21-induced browning of WAT in mice.

Schlessinger, Karni / Li, Wenyu / Tan, Yejun / Liu, Franklin / Souza, Sandra C / Tozzo, Effie / Liu, Kevin / Thompson, John R / Wang, Liangsu / Muise, Eric S

Obesity (Silver Spring, Md.)

2015 Volume 23, Issue 9, Page(s) 1818–1829

Abstract: Objective: Identify a gene expression signature in white adipose tissue (WAT) that reports on WAT browning and is associated with a healthy phenotype.: Methods: RNA from several different adipose depots across three species were analyzed by whole ... ...

Abstract	Objective: Identify a gene expression signature in white adipose tissue (WAT) that reports on WAT browning and is associated with a healthy phenotype. Methods: RNA from several different adipose depots across three species were analyzed by whole transcriptome profiling, including 1) mouse subcutaneous white fat, brown fat, and white fat after in vivo treatment with FGF21; 2) human subcutaneous and omental fat from insulin-sensitive and insulin-resistant patients; and 3) rhesus monkey subcutaneous fat from healthy and dysmetabolic individuals. Results: A "browning" signature in mice was identified by cross-referencing the FGF21-induced signature in WAT with the brown adipose tissue (BAT) vs. WAT comparison. In addition, gene expression levels in WAT from insulin-sensitive/healthy vs. insulin-resistant/dysmetabolic humans and rhesus monkeys, respectively, correlated with the gene expression levels in mouse BAT vs. WAT. A subset of 49 genes were identified that were consistently regulated or differentially expressed in the mouse and human data sets that could be used to monitor browning of WAT across species. Conclusions: Gene expression profiles of WATs from healthy insulin-sensitive individuals correlate with those of BAT and FGF21-induced browning of WAT.
MeSH term(s)	Adipose Tissue, Brown/metabolism ; Adipose Tissue, White/metabolism ; Animals ; Female ; Fibroblast Growth Factors/metabolism ; Gene Expression Profiling ; Haplorhini ; Humans ; Mice ; MicroRNAs/genetics ; Obesity/metabolism ; Subcutaneous Fat/metabolism ; Transcriptome
Chemical Substances	MicroRNAs ; fibroblast growth factor 21 ; Fibroblast Growth Factors (62031-54-3)
Language	English
Publishing date	2015-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2230457-5
ISSN	1930-739X ; 1071-7323 ; 1930-7381
ISSN (online)	1930-739X
ISSN	1071-7323 ; 1930-7381
DOI	10.1002/oby.21153
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 4061: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 87: Show issues

Order via subito

Details ▾

Article ; Online: Mitochondrial STAT3 supports Ras-dependent oncogenic transformation.

Gough, Daniel J / Corlett, Alicia / Schlessinger, Karni / Wegrzyn, Joanna / Larner, Andrew C / Levy, David E

Science (New York, N.Y.)

2009 Volume 324, Issue 5935, Page(s) 1713–1716

Abstract: Signal transducer and activator of transcription 3 (STAT3) is a latent cytoplasmic transcription factor responsive to cytokine signaling and tyrosine kinase oncoproteins by nuclear translocation when it is tyrosine-phosphorylated. We report that ... ...

Abstract	Signal transducer and activator of transcription 3 (STAT3) is a latent cytoplasmic transcription factor responsive to cytokine signaling and tyrosine kinase oncoproteins by nuclear translocation when it is tyrosine-phosphorylated. We report that malignant transformation by activated Ras is impaired without STAT3, in spite of the inability of Ras to drive STAT3 tyrosine phosphorylation or nuclear translocation. Moreover, STAT3 mutants that cannot be tyrosine-phosphorylated, that are retained in the cytoplasm, or that cannot bind DNA nonetheless supported Ras-mediated transformation. Unexpectedly, STAT3 was detected within mitochondria, and exclusive targeting of STAT3 to mitochondria without nuclear accumulation facilitated Ras transformation. Mitochondrial STAT3 sustained altered glycolytic and oxidative phosphorylation activities characteristic of cancer cells. Thus, in addition to its nuclear transcriptional role, STAT3 regulates a metabolic function in mitochondria, supporting Ras-dependent malignant transformation.
MeSH term(s)	Animals ; Cell Line ; Cell Line, Tumor ; Cell Nucleus/metabolism ; Cell Proliferation ; Cell Survival ; Cell Transformation, Neoplastic ; Genes, ras ; Glycolysis ; Membrane Potential, Mitochondrial ; Mice ; Mice, Inbred BALB C ; Mitochondria/metabolism ; Mutant Proteins/metabolism ; Neoplasms, Experimental/metabolism ; Neoplasms, Experimental/pathology ; Neoplastic Stem Cells ; Oxidative Phosphorylation ; Phosphorylation ; STAT3 Transcription Factor/genetics ; STAT3 Transcription Factor/metabolism ; Signal Transduction ; ras Proteins/metabolism
Chemical Substances	Mutant Proteins ; STAT3 Transcription Factor ; STAT3 protein, human ; ras Proteins (EC 3.6.5.2)
Language	English
Publishing date	2009-06-25
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	128410-1
ISSN	1095-9203 ; 0036-8075
ISSN (online)	1095-9203
ISSN	0036-8075
DOI	10.1126/science.1171721
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 27: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 77: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Phenotyping of adipose, liver, and skeletal muscle insulin resistance and response to pioglitazone in spontaneously obese rhesus monkeys.

American journal of physiology. Endocrinology and metabolism

2017 Volume 312, Issue 4, Page(s) E235–E243

Abstract: Insulin resistance and diabetes can develop spontaneously with obesity and aging in rhesus monkeys, highly similar to the natural history of obesity, insulin resistance, and progression to type 2 diabetes in humans. The current studies in obese rhesus ... ...

Abstract	Insulin resistance and diabetes can develop spontaneously with obesity and aging in rhesus monkeys, highly similar to the natural history of obesity, insulin resistance, and progression to type 2 diabetes in humans. The current studies in obese rhesus were undertaken to assess hepatic and adipose contributions to systemic insulin resistance-currently, a gap in our knowledge-and to benchmark the responses to pioglitazone (PIO). A two-step hyperinsulinemic-euglycemic clamp, with tracer-based glucose flux estimates, was used to measure insulin resistance, and in an intervention study was repeated following 6 wk of PIO treatment (3 mg/kg). Compared with lean healthy rhesus, obese rhesus has a 60% reduction of glucose utilization during a high insulin infusion and markedly impaired suppression of lipolysis, which was evident at both low and high insulin infusion. However, obese dysmetabolic rhesus manifests only mild hepatic insulin resistance. Six-week PIO treatment significantly improved skeletal muscle and adipose insulin resistance (by ~50%). These studies strengthen the concept that insulin resistance in obese rhesus closely resembles human insulin resistance and indicate the value of obese rhesus for appraising new insulin-sensitizing therapeutics.
MeSH term(s)	Adipose Tissue/drug effects ; Adipose Tissue/metabolism ; Animals ; Blood Glucose/metabolism ; Diabetes Mellitus, Type 2/drug therapy ; Diabetes Mellitus, Type 2/metabolism ; Glucose Clamp Technique ; Hypoglycemic Agents/pharmacology ; Hypoglycemic Agents/therapeutic use ; Insulin Resistance/physiology ; Lipolysis/physiology ; Liver/drug effects ; Liver/metabolism ; Macaca mulatta ; Muscle, Skeletal/drug effects ; Muscle, Skeletal/metabolism ; Obesity/drug therapy ; Obesity/metabolism ; Thiazolidinediones/pharmacology ; Thiazolidinediones/therapeutic use
Chemical Substances	Blood Glucose ; Hypoglycemic Agents ; Thiazolidinediones ; pioglitazone (X4OV71U42S)
Language	English
Publishing date	2017-04-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	603841-4
ISSN	1522-1555 ; 0193-1849
ISSN (online)	1522-1555
ISSN	0193-1849
DOI	10.1152/ajpendo.00398.2016
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Uc I Zs.89: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

To top

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Bonn / Germany

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito