Abstract
RGS19 is a regulator of G protein signaling which is upregulated in ovarian cancers and its overexpression promotes cell proliferation in several mammalian cell types. Here we showed that cyclin D1/3 and Cdk6 were upregulated in HEK293 cells overexpressing RGS19, while INK4A and INK4B were reduced. Moreover, RGS19 augmented serum-stimulated PTEN/PDK/Akt and Rb phosphorylations in 293/RGS19 and Caco2/RGS19 cells. These changes were reversed upon the knockdown of RGS19. Consistent with an elevated Akt activity, increased levels of phosphorylated Bad and c-Raf and a diminished expression of TSC2 were detected, thus demonstrating that RGS19 can deregulate cell proliferation via multiple pathways.
Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Cycle*
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Cell Proliferation*
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Cyclin D1 / biosynthesis
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Cyclin D1 / genetics
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Cyclin D3 / biosynthesis
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Cyclin D3 / genetics
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Cyclin-Dependent Kinase 6 / biosynthesis
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Cyclin-Dependent Kinase 6 / genetics
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Cyclin-Dependent Kinase Inhibitor p15
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Cyclin-Dependent Kinase Inhibitor p16
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HEK293 Cells
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HeLa Cells
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Humans
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PTEN Phosphohydrolase / metabolism
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Phosphorylation
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Protein Serine-Threonine Kinases / metabolism
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Proto-Oncogene Proteins c-akt / metabolism*
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Proto-Oncogene Proteins c-raf / biosynthesis
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Pyruvate Dehydrogenase Acetyl-Transferring Kinase
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RGS Proteins / biosynthesis
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RGS Proteins / genetics
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RGS Proteins / metabolism*
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RNA Interference
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RNA, Small Interfering
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Signal Transduction
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Tuberous Sclerosis Complex 2 Protein
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Tumor Suppressor Proteins / biosynthesis
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bcl-Associated Death Protein / biosynthesis
Substances
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BAD protein, human
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CDKN2B protein, human
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Cyclin D3
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Cyclin-Dependent Kinase Inhibitor p15
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Cyclin-Dependent Kinase Inhibitor p16
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Pyruvate Dehydrogenase Acetyl-Transferring Kinase
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RGS Proteins
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RNA, Small Interfering
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TSC2 protein, human
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Tuberous Sclerosis Complex 2 Protein
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Tumor Suppressor Proteins
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bcl-Associated Death Protein
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regulator of G-protein signalling 19
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Cyclin D1
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt
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Proto-Oncogene Proteins c-raf
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CDK6 protein, human
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Cyclin-Dependent Kinase 6
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PTEN Phosphohydrolase
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PTEN protein, human