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- Title
The phosphorylation state of an autoregulatory domain controls PACS-1-directed protein traffic.
- Authors
Gregory K. Scott; Feng Gu; Colin M. Crump; Laurel Thomas; Lei Wan; Yang Xiang; Gary Thomas
- Abstract
PACS-1 is a cytosolic sorting protein that directs the localization of membrane proteins in the trans-Golgi network (TGN)/endosomal system. PACS-1 connects the clathrin adaptor AP-1 to acidic cluster sorting motifs contained in the cytoplasmic domain of cargo proteins such as furin, the cation-independent mannose-6-phosphate receptor and in viral proteins such as human immunodeficiency virus type 1 Nef. Here we show that an acidic cluster on PACS-1, which is highly similar to acidic cluster sorting motifs on cargo molecules, acts as an autoregulatory domain that controls PACS-1-directed sorting. Biochemical studies show that Ser278 adjacent to the acidic cluster is phosphorylated by CK2 and dephosphorylated by PP2A. Phosphorylation of Ser278 by CK2 or a Ser278→Asp mutation increased the interaction between PACS-1 and cargo, whereas a Ser278→Ala substitution decreased this interaction. Moreover, the Ser278→Ala mutation yields a dominant-negative PACS-1 molecule that selectively blocks retrieval of PACS-1-regulated cargo molecules to the TGN. These results suggest that coordinated signaling events regulate transport within the TGN/endosomal system through the phosphorylation state of both cargo and the sorting machinery.
- Publication
EMBO Journal, 2003, Vol 22, Issue 23, p6234
- ISSN
0261-4189
- Publication type
Academic Journal
- DOI
10.1093/emboj/cdg596