Modulation of CREB activity by the Rho GTPase regulates cell and organism size during mouse embryonic development.
Journal:
Dev. Cell 2002 MayAuthors:
Sordella R, Classon M, Hu KQ, Matheson SF, Brouns MR, Fine B, Zhang L, Takami H, Yamada Y, Settleman J
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 exh
...[more]ibit 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.[less]
Mesh Headings:
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