FIG 9.

Adaptor binding and phosphorylation sites. The 53 amino acids constituting the cytoplasmic domain of sortilin and a summary of the known adaptor-binding sites, including the novel group A PAK-binding site, are shown. The extreme C terminus comprises an acidic cluster combined with a dileucine motif and constitutes a target site for binding of AP-1 and AP-2 complexes as well as GGA1-3. The upper juxtamembrane segment harbors at least two separate sites, one binding the retromer complex and the other binding AP-1 and AP-2. Our findings reveal that the two sites are furthermore part of yet another binding sequence that mediates interactions with the kinase domain of the group A PAKs. Serine residues that are targets for phosphorylation are marked in red, including the PAK phosphorylation sites Ser¹⁵ and Ser⁴⁷ in the GGA-binding site. TGN, trans-Golgi network.