Upon binding of EGF, the EGF receptor dimerizes and is activated (top right). Clathrin and other proteins
of the endocytotic machinery drive coated pit formation resulting in endocytosis of the EGF receptor and
the formation of an early endosome. EGF is released by acidification. The fate of the EGF receptor is
dependent on interactions with other proteins that result in transfer to endosomes in the perinuclear
region for recycling back to the cell surface or to the lysosome for degradation. A poly­proline region of
Reps1 is proposed to bind to the SH3 domains of Grb2/Crk adaptor proteins. In turn, their SH2 domains
bind the pY of activated EGF receptor, suggesting a complex containing both EGF receptor and Reps1.
The Reps1-Repsin interaction targets the EGF receptor to the recycling endosome. Rab11, a protein of the
recycling en­dosome binding the coiled-coil (CC) of Rep­sni (aan binds Rab11-FIP2)e. Reps1 also has
a coiled-coil, which forms the binding site for RalBP1, a protein that in turn binds Ral as part of the
Ras signaling pathway.