Journal article
Nedd4 Controls Animal Growth by Regulating IGF-1 Signaling
Science signaling, Vol.1(38), pp.ra5-ra5
09/23/2008
DOI: 10.1126/scisignal.1160940
PMCID: PMC2833362
PMID: 18812566
Abstract
The ubiquitin ligase Nedd4 has been proposed to regulate a number of signaling pathways, but its physiological role in mammals has not been characterized. Here we present an analysis of Nedd4-null mice to show that loss of Nedd4 results in reduced insulin-like growth factor 1 (IGF-1) and insulin signaling, delayed embryonic development, reduced growth and body weight, and neonatal lethality. In mouse embryonic fibroblasts, mitogenic activity was reduced, the abundance of the adaptor protein Grb10 was increased, and the IGF-1 receptor, which is normally present on the plasma membrane, was mislocalized. However, surface expression of IGF-1 receptor was restored in homozygous mutant mouse embryonic fibroblasts after knockdown of Grb10, and Nedd4(-/-) lethality was rescued by maternal inheritance of a disrupted Grb10 allele. Thus, in vivo, Nedd4 appears to positively control IGF-1 and insulin signaling partly through the regulation of Grb10 function.
Details
- Title: Subtitle
- Nedd4 Controls Animal Growth by Regulating IGF-1 Signaling
- Creators
- Xiao R. Cao - Univ Iowa, Carver Coll Med, Iowa City, IA 52242 USANancy L. Lill - Univ Iowa, Carver Coll Med, Iowa City, IA 52242 USANatasha Boase - Inst Med & Vet Sci, Hanson Inst, Adelaide, SA 5000, AustraliaPeijun P. Shi - Univ Iowa, Carver Coll Med, Iowa City, IA 52242 USADavid R. Croucher - Garvan Inst Med Res, Sydney, NSW 2010, AustraliaHongbo Shan - Univ Iowa, Carver Coll Med, Iowa City, IA 52242 USAJing Qu - Univ Iowa, Carver Coll Med, Iowa City, IA 52242 USAEileen M. Sweezer - Univ Iowa, Carver Coll Med, Iowa City, IA 52242 USATrenton Place - Univ Iowa, Carver Coll Med, Iowa City, IA 52242 USAPatricia A. Kirby - University of Iowa, PathologyRoger J. Daly - Garvan Inst Med Res, Sydney, NSW 2010, AustraliaSharad Kumar - Inst Med & Vet Sci, Hanson Inst, Adelaide, SA 5000, AustraliaBaoli Yang - University of Iowa, BioVentures Center
- Resource Type
- Journal article
- Publication Details
- Science signaling, Vol.1(38), pp.ra5-ra5
- DOI
- 10.1126/scisignal.1160940
- PMID
- 18812566
- PMCID
- PMC2833362
- NLM abbreviation
- Sci Signal
- ISSN
- 1945-0877
- eISSN
- 1937-9145
- Publisher
- Amer Assoc Advancement Science
- Number of pages
- 10
- Grant note
- P50DE016215 / NATIONAL INSTITUTE OF DENTAL &CRANIOFACIAL RESEARCH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Dental & Craniofacial Research (NIDCR) DE16215; P50 DE016215-059001 / NIDCR NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Dental & Craniofacial Research (NIDCR) AR052647 / NIAMS NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS) DK52617; P50 DK052617-100007 / NIDDK NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) P50DK052617 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK)
- Language
- English
- Date published
- 09/23/2008
- Academic Unit
- Pathology; BioVentures Center; Obstetrics and Gynecology
- Record Identifier
- 9983557216102771
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