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

Sordella, R., Classon, M., Hu, K. Q., Matheson, S. F., Brouns, M. R., Fine, B., Zhang, L., Takami, H., Yamada, Y., Settleman, J. (May 2002) Modulation of CREB activity by the Rho GTPase regulates cell and organism size during mouse embryonic development. Developmental Cell, 2 (5). pp. 553-65. ISSN 1534-5807

DOI: 10.1016/S1534-5807(02)00162-4


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.

Item Type: Paper
Uncontrolled 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 genetics metabolism Insulin metabolism Insulin Receptor Substrate Proteins Mice Mice, Knockout Mitogen-Activated Protein Kinases metabolism Models Biological Nuclear Proteins deficiency genetics metabolism Phenotype Phosphoproteins metabolism Phosphorylation Repressor Proteins Signal Transduction rho GTP-Binding Proteins metabolism
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > GTPase
organism description > animal
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > cell regulation
organism description > animal > developmental stage
organism description > animal > developmental stage > embryo
organism description > animal > mammal > rodent > mouse
CSHL Authors:
Communities: CSHL labs > Sordella lab
Depositing User: CSHL Librarian
Date: May 2002
Date Deposited: 09 May 2012 17:51
Last Modified: 13 Mar 2013 16:19
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