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Modulation of CREB activity by the Rho GTPase regulates cell and organism size during mouse embryonic development.

Developmental cell | May 17, 2002

http://www.ncbi.nlm.nih.gov/pubmed/12015964

Rho GTPases regulate several aspects of tissue morphogenesis during animal development. We found that mice lacking the Rho-inhibitory protein, p190-B RhoGAP, are 30% reduced in size and exhibit developmental defects strikingly similar to those seen in mice lacking the CREB transcription factor. In p190-B RhoGAP-deficient mice, CREB phosphorylation is substantially reduced in embryonic tissues. Embryo-derived cells contain abnormally high levels of active Rho protein, are reduced in size, and exhibit defects in CREB activation upon exposure to insulin or IGF-1. The cell size defect is rescued by expression of constitutively activated CREB, and in wild-type cells, expression of activated Rho or dominant-negative CREB results in reduced cell size. Together, these results suggest that activity of the Rho GTPase modulates a signal from insulin/IGFs to CREB that determines cell size and animal size during embryogenesis.

Pubmed ID: 12015964 RIS Download

Mesh terms: Animals | Body Constitution | Cell Size | Cyclic AMP Response Element-Binding Protein | DNA-Binding Proteins | Embryonic and Fetal Development | GTPase-Activating Proteins | Guanine Nucleotide Exchange Factors | Insulin | Insulin Receptor Substrate Proteins | Mice | Mice, Knockout | Mitogen-Activated Protein Kinases | Models, Biological | Nuclear Proteins | Phenotype | Phosphoproteins | Phosphorylation | Repressor Proteins | Signal Transduction | rho GTP-Binding Proteins

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Mouse Genome Informatics (Data, Gene Annotation)

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