Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
E-selectin ligand-1 regulates growth plate homeostasis in mice by inhibiting the intracellular processing and secretion of mature TGF-beta.
Yang T, Mendoza-Londono R, Lu H, Tao J, Li K, Keller B, Jiang MM, Shah R, Chen Y, Bertin TK, Engin F, Dabovic B, Rifkin DB, Hicks J, Jamrich M, Beaudet AL, Lee B.
???displayArticle.abstract???
The majority of human skeletal dysplasias are caused by dysregulation of growth plate homeostasis. As TGF-beta signaling is a critical determinant of growth plate homeostasis, skeletal dysplasias are often associated with dysregulation of this pathway. The context-dependent action of TFG-beta signaling is tightly controlled by numerous mechanisms at the extracellular level and downstream of ligand-receptor interactions. However, TGF-beta is synthesized as an inactive precursor that is cleaved to become mature in the Golgi apparatus, and the regulation of this posttranslational intracellular processing and trafficking is much less defined. Here, we report that a cysteine-rich protein, E-selectin ligand-1 (ESL-1), acts as a negative regulator of TGF-beta production by binding TGF-beta precursors in the Golgi apparatus in a cell-autonomous fashion, inhibiting their maturation. Furthermore, ESL-1 inhibited the processing of proTGF-beta by a furin-like protease, leading to reduced secretion of mature TGF-beta by primary mouse chondrocytes and HEK293 cells. In vivo loss of Esl1 in mice led to increased TGF-beta/SMAD signaling in the growth plate that was associated with reduced chondrocyte proliferation and delayed terminal differentiation. Gain-of-function and rescue studies of the Xenopus ESL-1 ortholog in the context of early embryogenesis showed that this regulation of TGF-beta/Nodal signaling was evolutionarily conserved. This study identifies what we believe to be a novel intracellular mechanism for regulating TGF-beta during skeletal development and homeostasis.
Abe,
An assay for transforming growth factor-beta using cells transfected with a plasminogen activator inhibitor-1 promoter-luciferase construct.
1994, Pubmed
Abe,
An assay for transforming growth factor-beta using cells transfected with a plasminogen activator inhibitor-1 promoter-luciferase construct.
1994,
Pubmed Ahn,
A novel isoform of human Golgi complex-localized glycoprotein-1 (also known as E-selectin ligand-1, MG-160 and cysteine-rich fibroblast growth factor receptor) targets differential subcellular localization.
2005,
Pubmed Alvarez,
TGFbeta2 mediates the effects of hedgehog on hypertrophic differentiation and PTHrP expression.
2002,
Pubmed Alvarez,
The perichondrium plays an important role in mediating the effects of TGF-beta1 on endochondral bone formation.
2001,
Pubmed Annes,
Making sense of latent TGFbeta activation.
2003,
Pubmed Burrus,
Identification of a cysteine-rich receptor for fibroblast growth factors.
1992,
Pubmed Dabovic,
Bone abnormalities in latent TGF-[beta] binding protein (Ltbp)-3-null mice indicate a role for Ltbp-3 in modulating TGF-[beta] bioavailability.
2002,
Pubmed Deng,
Fibroblast growth factor receptor 3 is a negative regulator of bone growth.
1996,
Pubmed Di Nino,
Multiple mechanisms of perichondrial regulation of cartilage growth.
2002,
Pubmed Di Nino,
Regulation of endochondral cartilage growth in the developing avian limb: cooperative involvement of perichondrium and periosteum.
2001,
Pubmed Dubois,
Processing of transforming growth factor beta 1 precursor by human furin convertase.
1995,
Pubmed Gumienny,
The other side of TGF-beta superfamily signal regulation: thinking outside the cell.
2002,
Pubmed Hensel,
A novel proliferation-associated variant of CFR-1 defined by a human monoclonal antibody.
2001,
Pubmed Hidalgo,
Complete identification of E-selectin ligands on neutrophils reveals distinct functions of PSGL-1, ESL-1, and CD44.
2007,
Pubmed Keene,
Fibrillin-1 in human cartilage: developmental expression and formation of special banded fibers.
1997,
Pubmed Koo,
ADAMTS-like 2 (ADAMTSL2) is a secreted glycoprotein that is widely expressed during mouse embryogenesis and is regulated during skeletal myogenesis.
2007,
Pubmed Kronenberg,
PTHrP and skeletal development.
2006,
Pubmed Kronenberg,
The role of the perichondrium in fetal bone development.
2007,
Pubmed Kronenberg,
Developmental regulation of the growth plate.
2003,
Pubmed Le Goff,
ADAMTSL2 mutations in geleophysic dysplasia demonstrate a role for ADAMTS-like proteins in TGF-beta bioavailability regulation.
2008,
Pubmed Miyazono,
Retention of the transforming growth factor-beta 1 precursor in the Golgi complex in a latent endoglycosidase H-sensitive form.
1992,
Pubmed Miyazono,
A role of the latent TGF-beta 1-binding protein in the assembly and secretion of TGF-beta 1.
1991,
Pubmed Murakami,
Constitutive activation of MEK1 in chondrocytes causes Stat1-independent achondroplasia-like dwarfism and rescues the Fgfr3-deficient mouse phenotype.
2004,
Pubmed Ohbayashi,
FGF18 is required for normal cell proliferation and differentiation during osteogenesis and chondrogenesis.
2002,
Pubmed Olofsson,
Latent transforming growth factor-beta complex in Chinese hamster ovary cells contains the multifunctional cysteine-rich fibroblast growth factor receptor, also termed E-selectin-ligand or MG-160.
1997,
Pubmed Pelton,
In situ hybridization analysis of TGF beta 3 RNA expression during mouse development: comparative studies with TGF beta 1 and beta 2.
1990,
Pubmed Roberts,
Meeting report: signaling schemes for TGF-beta.
2001,
Pubmed
,
Xenbase Roth-Eichhorn,
Subcellular localization of (latent) transforming growth factor beta and the latent TGF-beta binding protein in rat hepatocytes and hepatic stellate cells.
1998,
Pubmed Serra,
TGF-beta signaling in human skeletal and patterning disorders.
2003,
Pubmed Shiang,
Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia.
1994,
Pubmed Steegmaier,
The E-selectin-ligand ESL-1 is a variant of a receptor for fibroblast growth factor.
1995,
Pubmed Tao,
BMP4-dependent expression of Xenopus Grainyhead-like 1 is essential for epidermal differentiation.
2005,
Pubmed
,
Xenbase Tavella,
Targeted expression of SHH affects chondrocyte differentiation, growth plate organization, and Sox9 expression.
2004,
Pubmed Thomas,
Furin at the cutting edge: from protein traffic to embryogenesis and disease.
2002,
Pubmed Tseng,
Function and regulation of FoxF1 during Xenopus gut development.
2004,
Pubmed
,
Xenbase Yokota,
A novel role for a nodal-related protein; Xnr3 regulates convergent extension movements via the FGF receptor.
2003,
Pubmed
,
Xenbase Zacchigna,
Emilin1 links TGF-beta maturation to blood pressure homeostasis.
2006,
Pubmed
,
Xenbase
