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Fig. 1. Endofin binds to Smad1 (Shi et al., 2007 ), and the BMP type-I receptors ALK3 and 6 (Chen et al., 2007). However, endofin is localized on the early endocytic compartment implying that internalization of the ligand-receptor complex is required for Smad1 phosphorylation. As there is evidence that Smad1 phosphorylation is internalization independent (Hartung et al., 2006), small amounts of endofin might also be present on the plasma membrane (?) bound to ALK3 and/or ALK6. It should be noted that, although SARA is localized on early endosomes, it is also found at the plasma membrane bound to TGF- receptor II (Tsukazaki et al., 1998). Furthermore, endofin recruits PP1c via GADD34 (which also binds ALK3) causing dephosphorylation of the BMP type-I receptor. Location of the endofin-PPIc complex is still unresolved - here it is depicted on the endosomal compartment and also at the plasma membrane (?) - and other effectors could also target PPIc to the latter. Endofin also binds Smad4, here shown on the endosome (Chen et al., 2007). The possible involvement of endofin in degradation of the receptors is depicted on the surface of the endosome by recruitment of TOM1 and clathrin.
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