Role of RGS-PX1 in G Protein Signaling and Endocytosis

The RGS proteins constitute a family (~30) that serve as GAPs for heterotrimeric G proteins, with different family members serving as GAPs for different G alpha subunits. Typically RGS proteins contain a variety of domains and motifs that connect G protein signaling to a multiplicity of cell functions and signaling pathways. RGS-PX1, like other RGS family members, contains several different domains-- PX and PX1 domains--as well as an RGS domain and serves to link G protein signaling to growth factor signaling. It acts as both a GAP for the Gαs through its RGS domain and as a SNX (sorting nexin) through its PX domain. We have shown that it potentiates EGF receptor signaling by slowing degradation of the EGF receptor at the level of the endosome. We are now further characterizing RGSPX1 and its role in signaling. In particular we are trying to work out the flow of information along the RGS-PX1 signaling network and the trafficking of RGS-PX1 and the molecular mechanisms whereby it participates in the regulation of EGF receptor trafficking and signaling.

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