spacer gif spacer gif spacer gif spacer gif ARCHIVE ANNOUNCEMENT! spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents    

First published online December 12, 2006
doi: 10.1242/10.1242/dev.02701

Development 134, 167-176 (2007)
Published by The Company of Biologists 2007
This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Li, C.
Right arrow Articles by Mansour, S. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Li, C.
Right arrow Articles by Mansour, S. L.

Dusp6 (Mkp3) is a negative feedback regulator of FGF-stimulated ERK signaling during mouse development

Chaoying Li1, Daryl A. Scott1,*, Ekaterina Hatch1, Xiaoyan Tian2 and Suzanne L. Mansour1,{dagger}

1 Department of Human Genetics, University of Utah, 15 N 2030 E RM 2100, Salt Lake City, UT 84112-5330, USA.
2 Division of Radiobiology, University of Utah, 729 Arapeen Drive #2334, Salt Lake City, UT 84108-1218, USA.

{dagger} Author for correspondence (e-mail: suzi.mansour{at}genetics.utah.edu)

Accepted 17 October 2006

Mitogen-activated protein kinase (MAPK) pathways are major mediators of extracellular signals that are transduced to the nucleus. MAPK signaling is attenuated at several levels, and one class of dual-specificity phosphatases, the MAPK phosphatases (MKPs), inhibit MAPK signaling by dephosphorylating activated MAPKs. Several of the MKPs are themselves induced by the signaling pathways they regulate, forming negative feedback loops that attenuate the signals. We show here that in mouse embryos, Fibroblast growth factor receptors (FGFRs) are required for transcription of Dusp6, which encodes MKP3, an extracellular signal-regulated kinase (ERK)-specific MKP. Targeted inactivation of Dusp6 increases levels of phosphorylated ERK, as well as the pERK target, Erm, and transcripts initiated from the Dusp6 promoter itself. Finally, the Dusp6 mutant allele causes variably penetrant, dominant postnatal lethality, skeletal dwarfism, coronal craniosynostosis and hearing loss; phenotypes that are also characteristic of mutations that activate FGFRs inappropriately. Taken together, these results show that DUSP6 serves in vivo as a negative feedback regulator of FGFR signaling and suggest that mutations in DUSP6 or related genes are candidates for causing or modifying unexplained cases of FGFR-like syndromes.

Key words: Mkp3, Pyst1, Dual specificity phosphatase, Craniosynostosis, Middle ear, Otic capsule, Mouse




This article has been cited by other articles:


Home page
 Mol. Biol. CellHome page
O. V. Mortensen, M. B. Larsen, B. M. Prasad, and S. G. Amara
Genetic Complementation Screen Identifies a Mitogen-activated Protein Kinase Phosphatase, MKP3, as a Regulator of Dopamine Transporter Trafficking
Mol. Biol. Cell, July 1, 2008; 19(7): 2818 - 2829.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
H.-Y. Fan, M. Shimada, Z. Liu, N. Cahill, N. Noma, Y. Wu, J. Gossen, and J. S. Richards
Selective expression of KrasG12D in granulosa cells of the mouse ovary causes defects in follicle development and ovulation
Development, June 15, 2008; 135(12): 2127 - 2137.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
L. M. Cotton, M. K. O'Bryan, and B. T. Hinton
Cellular Signaling by Fibroblast Growth Factors (FGFs) and Their Receptors (FGFRs) in Male Reproduction
Endocr. Rev., April 1, 2008; 29(2): 193 - 216.
[Abstract] [Full Text] [PDF]


© The Company of Biologists Ltd 2007