Endocytosis participates in downregulating incoming signals, but 'signaling endosomes' may also serve as physical platforms for crosstalk between signaling pathways. Here, we briefly review the role of endosomes in signaling crosstalk and suggest that endosome-associated scaffold proteins mediate this crosstalk. In addition, using a proteome-wide in silico approach - in which we analyze endosome-binding properties and the capacity of candidates to recruit signaling proteins from more than one distinct pathway - we extend the list of putative crosstalk-mediating endosomal scaffolds. Because endosomal crosstalk may be an important systems-level regulator of pathway communication, scaffold proteins that mediate this crosstalk could be potential targets for pharmacological intervention and synthetic engineering.
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