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XB-ART-45722
Open Biol April 1, 2012; 2 (4): 120060.

Eps15R is required for bone morphogenetic protein signalling and differentially compartmentalizes with Smad proteins.

Callery EM , Park CY , Xu X , Zhu H , Smith JC , Thomsen GH .


Abstract
Transforming growth factor β superfamily members signal through Smad transcription factors. Bone morphogenetic proteins (BMPs) act via Smads 1, 5 and 8 and TGF-βs signal through Smads 2 and 3. The endocytic adaptor protein Eps15R, or ''epidermal growth factor (EGF) receptor pathway substrate 15-related protein'' is a component of EGF signal transduction, mediating internalization of the EGF receptor. We show that it interacts with Smad proteins, is required for BMP signalling in animal caps and stimulates Smad1 transcriptional activity. This function resides in the Asp-Pro-Phe motif-enriched ''DPF domain'' of Eps15R, which activates transcription and antagonizes Smad2 signalling. In living cells, Eps15R segregates into spatially distinct regions with different Smads, indicating an unrecognized level of Smad compartmentalization.

PubMed ID: 22724065
PMC ID: PMC3376731
Article link: Open Biol
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: bmp4 cfp chrd.1 egf eps15 eps15l1 evx1 fgf4 frzb gnpda1 gpi gsc h2bc21 hba1 myc odc1 smad1 smad2 tbxt
Morpholinos: eps15l1 MO1

Phenotypes: Xla Wt + eps15l1 (fig.2.b) [+]

Article Images: [+] show captions
References [+] :
Bean, Hrs-2 regulates receptor-mediated endocytosis via interactions with Eps15. 2000, Pubmed