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

Raffaella Sordella; Marie Classon; Kang Quan Hu; Stephen F Matheson; Madeleine R Brouns; Barry Fine; Le Zhang; Hiroya Takami; Yoshihiko Yamada; Jeffrey Settleman

doi:10.1016/s1534-5807(02)00162-4

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

Dev Cell. 2002 May;2(5):553-65. doi: 10.1016/s1534-5807(02)00162-4.

Authors

Raffaella Sordella¹, Marie Classon, Kang Quan Hu, Stephen F Matheson, Madeleine R Brouns, Barry Fine, Le Zhang, Hiroya Takami, Yoshihiko Yamada, Jeffrey Settleman

Affiliation

¹ MGH Cancer Center and Harvard Medical School, Charlestown, MA 02129, USA.

PMID: 12015964
DOI: 10.1016/s1534-5807(02)00162-4

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.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

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*

Substances

Arhgap35 protein, mouse
Arhgap5 protein, mouse
Cyclic AMP Response Element-Binding Protein
DNA-Binding Proteins
GTPase-Activating Proteins
Guanine Nucleotide Exchange Factors
Insulin
Insulin Receptor Substrate Proteins
Irs1 protein, mouse
Nuclear Proteins
Phosphoproteins
Repressor Proteins
Mitogen-Activated Protein Kinases
rho GTP-Binding Proteins