Cdc42GAP regulates c-Jun N-terminal kinase (JNK)-mediated apoptosis and cell number during mammalian perinatal growth |
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| Authors: | Wang Lei Yang Linda Burns Kevin Kuan Chia-Yi Zheng Yi |
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| Affiliation: | Division of Experimental Hematology, Children's Hospital Medical Center, Molecular Developmental Biology Graduate Program, University of Cincinnati, Cincinnati, OH 45229, USA. |
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| Abstract: | Rho family GTPase Cdc42 is known to regulate polarity and growth in lower eukaryotes, but its physiologic function in mammals has yet to be determined. Here we have disrupted cdc42gap, a ubiquitously expressed negative regulator of Cdc42, in mice. Cdc42GAP(-/-) embryonic fibroblasts and various organs displayed significantly elevated Cdc42 activity. The embryonic and neonatal homozygous mice were reduced in size by approximately 25-40% and suffered severe growth retardation. Major organs from Cdc42GAP(-/-) mice were proportionally smaller because of decreased cell number. Basal apoptosis was increased in Cdc42GAP(-/-) cells and tissues, and this was attributed to altered c-Jun N-terminal kinase apoptotic signals. These results reveal a role of Cdc42GAP in mammalian perinatal growth and implicate the c-Jun N-terminal kinase-mediated apoptosis machinery as a Cdc42 effector pathway in vivo. |
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