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A PACS-1, GGA3 and CK2 complex regulates CI-MPR trafficking.
- Source :
-
The EMBO journal [EMBO J] 2006 Oct 04; Vol. 25 (19), pp. 4423-35. Date of Electronic Publication: 2006 Sep 14. - Publication Year :
- 2006
-
Abstract
- The cation-independent mannose-6-phosphate receptor (CI-MPR) follows a highly regulated sorting itinerary to deliver hydrolases from the trans-Golgi network (TGN) to lysosomes. Cycling of CI-MPR between the TGN and early endosomes is mediated by GGA3, which directs TGN export, and PACS-1, which directs endosome-to-TGN retrieval. Despite executing opposing sorting steps, GGA3 and PACS-1 bind to an overlapping CI-MPR trafficking motif and their sorting activity is controlled by the CK2 phosphorylation of their respective autoregulatory domains. However, how CK2 coordinates these opposing roles is unknown. We report a CK2-activated phosphorylation cascade controlling PACS-1- and GGA3-mediated CI-MPR sorting. PACS-1 links GGA3 to CK2, forming a multimeric complex required for CI-MPR sorting. PACS-1-bound CK2 stimulates GGA3 phosphorylation, releasing GGA3 from CI-MPR and early endosomes. Bound CK2 also phosphorylates PACS-1Ser(278), promoting binding of PACS-1 to CI-MPR to retrieve the receptor to the TGN. Our results identify a CK2-controlled cascade regulating hydrolase trafficking and sorting of itinerant proteins in the TGN/endosomal system.
- Subjects :
- Amino Acid Sequence
Animals
Cattle
Enzyme Activation
HeLa Cells
Humans
Molecular Sequence Data
Mutant Proteins metabolism
Phosphorylation
Protein Binding
Protein Transport
Rats
Receptor, IGF Type 2 chemistry
Swine
Vaccinia virus physiology
Vesicular Transport Proteins chemistry
trans-Golgi Network metabolism
ADP-Ribosylation Factors metabolism
Adaptor Proteins, Vesicular Transport metabolism
Casein Kinase II metabolism
Receptor, IGF Type 2 metabolism
Vesicular Transport Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0261-4189
- Volume :
- 25
- Issue :
- 19
- Database :
- MEDLINE
- Journal :
- The EMBO journal
- Publication Type :
- Academic Journal
- Accession number :
- 16977309
- Full Text :
- https://doi.org/10.1038/sj.emboj.7601336