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PMID:12015964
| Citation |
Sordella, R, Classon, M, Hu, KQ, Matheson, SF, Brouns, MR, Fine, B, Zhang, L, Takami, H, Yamada, Y and Settleman, J (2002) Modulation of CREB activity by the Rho GTPase regulates cell and organism size during mouse embryonic development. Dev. Cell 2:553-65 |
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| Abstract |
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. |
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| Keywords |
Animals; Body Constitution; Cell Size; Cyclic AMP Response Element-Binding Protein/metabolism; DNA-Binding Proteins; Embryonic and Fetal Development; GTPase-Activating Proteins; Guanine Nucleotide Exchange Factors/deficiency; Guanine Nucleotide Exchange Factors/genetics; Guanine Nucleotide Exchange Factors/metabolism; Insulin/metabolism; Insulin Receptor Substrate Proteins; Mice; Mice, Knockout; Mitogen-Activated Protein Kinases/metabolism; Models, Biological; Nuclear Proteins/deficiency; Nuclear Proteins/genetics; Nuclear Proteins/metabolism; Phenotype; Phosphoproteins/metabolism; Phosphorylation; Repressor Proteins; Signal Transduction; rho GTP-Binding Proteins/metabolism |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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