The cytoplasmic tail of the cation-independent mannose 6-phosphate receptor contains four binding sites for AP-1.
The trafficking of the cation-independent mannose 6-phosphate receptor between the trans-Golgi network and endosomes requires binding of sorting determinants in the cytoplasmic tail of the receptor to adaptor protein complex-1 (AP-1). Using a GST pull-down binding assay, four binding motifs were identified in the cytoplasmic tail: a tyrosine-based motif ((26)YSKV(29)), an internal dileucine-based motif ((39)ETEWLM(44)), and two casein kinase 2 sites ((84)DSEDE(88) and (154)DDSDED(159)). The YSKV motif mediated the strongest interaction with AP-1 and the two CK2 motifs bound AP-1 only when they were phosphorylated. The COOH-terminal dileucines were not required for interaction with AP-1.
Ghosh
Pradipta
P
Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Kornfeld
Stuart
S
D033961:Adaptor Protein Complex 1 / Q000737:chemistry* / Q000378:metabolism*; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001665:Binding Sites; D003593:Cytoplasm / Q000737:chemistry* / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D017527:Receptor, IGF Type 2 / Q000737:chemistry* / Q000378:metabolism*; D013329:Structure-Activity Relationship
D033961:Adaptor Protein Complex 1; D017527:Receptor, IGF Type 2