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Biochemistry, Biophysics, and Structural Biology Commons

Open Access. Powered by Scholars. Published by Universities.®

Physiology

2011

Animals; Bone Development; Disease Models, Animal; Dwarfism; Enzyme Activation; Face; Female; Gene Knock-In Techniques; Genetic Diseases, X-Linked; Genitalia, Male; Guanine Nucleotide Exchange Factors; Hand Deformities, Congenital; Heart Defects, Congenital; Humans; MAP Kinase Kinase Kinases; MAP Kinase Signaling System; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Mutant Strains; *Mutation; Osteoblasts; Proteins; cdc42 GTP-Binding Protein; p38 Mitogen-Activated Protein Kinases

Articles 1 - 1 of 1

Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Mlk3 Regulates Bone Development Downstream Of The Faciogenital Dysplasia Protein Fgd1 In Mice, Weiguo Zou, Matthew B. Greenblatt, Jae-Hyuck Shim, Shashi Kant, Bo Zhai, Sutada Lotinun, Nicholas Brady, Dorothy Zhang Hu, Steven P. Gygi, Roland Baron, Roger J. Davis, Dallas Jones, Laurie H. Glimcher Nov 2011

Mlk3 Regulates Bone Development Downstream Of The Faciogenital Dysplasia Protein Fgd1 In Mice, Weiguo Zou, Matthew B. Greenblatt, Jae-Hyuck Shim, Shashi Kant, Bo Zhai, Sutada Lotinun, Nicholas Brady, Dorothy Zhang Hu, Steven P. Gygi, Roland Baron, Roger J. Davis, Dallas Jones, Laurie H. Glimcher

Davis Lab Publications

Mutations in human FYVE, RhoGEF, and PH domain-containing 1 (FGD1) cause faciogenital dysplasia (FGDY; also known as Aarskog syndrome), an X-linked disorder that affects multiple skeletal structures. FGD1 encodes a guanine nucleotide exchange factor (GEF) that specifically activates the Rho GTPase CDC42. However, the mechanisms by which mutations in FGD1 affect skeletal development are unknown. Here, we describe what we believe to be a novel signaling pathway in osteoblasts initiated by FGD1 that involves the MAP3K mixed-lineage kinase 3 (MLK3). We observed that MLK3 functions downstream of FGD1 to regulate ERK and p38 MAPK, which in turn phosphorylate and activate ...