| The small GTPase Rac suppresses apoptosis caused by serum deprivation in fibroblasts. | |
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MedLine Citation:
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PMID: 11474575 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: The small GTPase Rac1 is a key signaling protein that mediates a number of important physiologic functions including the organization of the actin cytoskeleton, lipid metabolism, and gene transcription. Rac1 has also been implicated in oncogenic transformation. Expression of constitutively active Rac1 in Rat1 fibroblasts elicits serum- and anchorage-independent growth and causes tumorigenicity in nude mice. The signaling pathways that mediate the role of Rac in cell transformation remain to be identified. Here, we study the role of Rac in cell survival in the absence of serum. MATERIALS AND METHODS: The cell lines used in this study are Ratl fibroblasts that express constitutively active or dominant negative mutants of Rac1. We used long-term video time-lapse microscopy to analyze the effects of these Rac1 mutants on mitogenicity and apoptosis. RESULTS: We show that the increase in viability, which is stimulated by Rac1 in the absence of serum, is predominantly caused by an inhibition of apoptosis, with a minor increase in cell division. We also show that Rac1-stimulated cell viability in serum-starved cells is inhibited by chemical inhibition of phosphatidylinositol 3-kinase. CONCLUSIONS: Our observations indicate a role for Rac1 in survival signaling, possibly via activation of phosphatidylinositol 3-kinase. We propose that Rac1-stimulated cell survival may contribute to the role of Rac1 in serum-independent growth and cell transformation. |
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Authors:
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R Ruggieri; Y Y Chuang; M Symons |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Molecular medicine (Cambridge, Mass.) Volume: 7 ISSN: 1076-1551 ISO Abbreviation: Mol. Med. Publication Date: 2001 May |
Date Detail:
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Created Date: 2001-07-27 Completed Date: 2001-12-05 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 9501023 Medline TA: Mol Med Country: United States |
Other Details:
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Languages: eng Pagination: 293-300 Citation Subset: IM |
Affiliation:
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Onyx Pharmaceuticals, Richmond, CA, USA. mruggieri@picower.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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1-Phosphatidylinositol 3-Kinase
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antagonists & inhibitors,
metabolism* Animals Apoptosis / physiology* Cell Division / physiology Cell Survival / physiology Cells, Cultured Culture Media, Serum-Free / metabolism Enzyme-Linked Immunosorbent Assay Fibroblasts / cytology, enzymology* GTPase-Activating Proteins / antagonists & inhibitors* Genes, Reporter Immune Sera In Situ Nick-End Labeling JNK Mitogen-Activated Protein Kinases* MAP Kinase Kinase 4 Microscopy, Video Mitogen-Activated Protein Kinase Kinases / physiology Mutation Phosphorylation Protein Binding Rats Signal Transduction rac1 GTP-Binding Protein / antagonists & inhibitors, physiology* |
| Chemical | |
Reg. No./Substance:
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0/Culture Media, Serum-Free; 0/GTPase-Activating Proteins; 0/Immune Sera; EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase; EC 2.7.11.24/JNK Mitogen-Activated Protein Kinases; EC 2.7.12.2/MAP Kinase Kinase 4; EC 2.7.12.2/Mitogen-Activated Protein Kinase Kinases; EC 3.6.5.2/rac1 GTP-Binding Protein |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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