Eps15R is required for bone morphogenetic protein signalling and differentially compartmentalizes with Smad proteins.
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.
Department of Medicine, University of Cambridge, PO Box 157, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK. emc13@cam.ac.uk
Elizabeth M
EM
Callery
Chong Yon
CY
Park
Xin
X
Xu
Haitao
H
Zhu
James C
JC
Smith
Gerald H
GH
Thomsen
D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D030801:Animals, Genetically Modified; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002451:Cell Compartmentation; D066246:ErbB Receptors / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism*; D051898:Smad1 Protein / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D029867:Xenopus Proteins / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; D011993:Recombinant Fusion Proteins; D051785:Smad Proteins; D051898:Smad1 Protein; D029867:Xenopus Proteins; D066246:ErbB Receptors