Gremlin1 preferentially binds to Bone Morphogenetic Protein-2 (BMP-2) and BMP-4 over BMP-7
Data(s) |
15/02/2015
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Resumo |
Gremlin (Grem1) is a member of the DAN family of secreted bone morphogenetic protein (BMP) antagonists. Bone morphogenetic protein-7 (BMP-7) mediates protective effects during renal fibrosis-associated with diabetes and other renal diseases. The pathogenic mechanism of Grem1 during DN has been suggested to be binding and inhibition of BMP-7. However, the precise interactions between Grem1, BMP-7 and other BMPs have not been accurately defined. Here we show the affinity of Grem1 for BMP-7 is lower than that of BMP-2 and BMP-4, using a combination of surface plasmon resonance and cell culture techniques. Using kidney proximal tubule cells and HEK-293 cell Smad1/5/8 phosphorylation and BMP-dependent gene expression as readout, Grem1 consistently demonstrated a higher affinity for BMP-2>4>7. Cell-associated Grem1 did not inhibit BMP-2 or BMP-4 mediated signalling, suggesting that Grem1-BMP-2 binding occurred in solution, preventing BMP receptor activation. These data suggest that Grem1 preferentially binds to BMP-2 and this may be the dominant complex in a disease situation where levels of Grem1 and BMPs are elevated. |
Formato |
application/pdf |
Identificador | |
Idioma(s) |
eng |
Direitos |
info:eu-repo/semantics/openAccess |
Fonte |
Church , R H , Krishnakumar , A , Urbanek , A , Geschwinder , S , Meneely , J , Bianchi , A , Basta , B , Monaghan , S , Elliott , C , Stromstedt , M , Ferguson , N , Martin , F & Brazil , D P 2015 , ' Gremlin1 preferentially binds to Bone Morphogenetic Protein-2 (BMP-2) and BMP-4 over BMP-7 ' Biochemical Journal , vol 466 , no. 1 , pp. 55-68 . DOI: 10.1042/BJ20140771 |
Tipo |
article |