Regulation of endosome sorting by a specific PP2A isoform

被引:85
作者
Molloy, SS
Thomas, L
Kamibayashi, C
Mumby, MC
Thomas, G
机构
[1] Oregon Hlth & Sci Univ, Vollum Inst, Portland, OR 97201 USA
[2] Univ Texas, SW Med Ctr, Dept Pharmacol, Dallas, TX 75235 USA
关键词
furin; endosome; PP2A; sorting; PACS-1;
D O I
10.1083/jcb.142.6.1399
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The regulated sorting of proteins within the trans-Golgi network (TGN)/endosomal system is a key determinant of their biological activity in vivo. For example, the endoprotease furin activates of a wide range of proproteins in multiple compartments within the TGN/endosomal system. Phosphorylation of its cytosolic domain by casein kinase II (CKII) promotes the localization of furin to the TGN and early endosomes whereas dephosphorylation is required for efficient transport between these compartments (Jones, B,G., L. Thomas, S.S. Molloy, C.D. Thulin, M.D. Fry, K.A. Walsh, and G. Thomas. 1995. EMBO [Eur. Mol. Biol. Organ.] J. 14:5869-5883). Here we show that phosphorylated furin molecules internalized from the cell surface are retained in a local cycling loop between early endosomes and the plasma membrane. This cycling loop requires the phosphorylation state-dependent furin-sorting protein PACS-1, and mirrors the trafficking pathway described recently for the TGN localization of furin (Wan, L., S.S. Molloy, L. Thomas, G. Liu, Y. Xiang, S.L. Ryback, and G. Thomas. 1998. Cell. 94:205-216). We also demonstrate a novel role for protein phosphatase 2A (PP2A) in regulating protein localization in the TGN/endosomal system. Using baculovirus recombinants expressing individual PP2A subunits, we show that the dephosphorylation of furin in vitro requires heterotrimeric phosphatase containing B family regulatory subunits. The importance of this PP2A isoform in directing the routing of furin from early endosomes to the TGN was established using SV-40 small t antigen as a diagnostic tool in vivo. The role of both CKII and PP2A in controlling multiple sorting steps in the TGN/endosomal system indicates that the distribution of itinerant membrane proteins may be acutely regulated via signal transduction pathways.
引用
收藏
页码:1399 / 1411
页数:13
相关论文
共 90 条
[1]   A tyrosine-based motif and a casein kinase II phosphorylation site regulate the intracellular trafficking of the varicella-zoster virus glycoprotein I, a protein localized in the trans-Golgi network [J].
Alconada, A ;
Bauer, U ;
Hoflack, B .
EMBO JOURNAL, 1996, 15 (22) :6096-6110
[2]   PROTEIN KINASES .4. PROTEIN-KINASE CK2 - AN ENZYME WITH MULTIPLE SUBSTRATES AND A PUZZLING REGULATION [J].
ALLENDE, JE ;
ALLENDE, CC .
FASEB JOURNAL, 1995, 9 (05) :313-323
[3]  
APODACA G, 1993, J BIOL CHEM, V268, P23712
[4]   Reconstitution of transcytosis in SLO-permeabilized MDCK cells: Existence of an NSF-dependent fusion mechanism with the apical surface of MDCK cells [J].
Apodaca, G ;
Cardone, MH ;
Whiteheart, SW ;
DasGupta, BR ;
Mostov, KE .
EMBO JOURNAL, 1996, 15 (07) :1471-1481
[5]   Formation of nascent secretory vesicles from the trans-golgi network of endocrine cells is inhibited by tyrosine kinase and phosphatase inhibitors [J].
Austin, CD ;
Shields, D .
JOURNAL OF CELL BIOLOGY, 1996, 135 (06) :1471-1483
[6]   Molecular mechanisms of the protein serine threonine phosphatases [J].
Barford, D .
TRENDS IN BIOCHEMICAL SCIENCES, 1996, 21 (11) :407-412
[7]   SELECTIVE ACTIVATION OF THE RAT HEPATIC ENDOSOMAL INSULIN-RECEPTOR KINASE - ROLE FOR THE ENDOSOME IN INSULIN SIGNALING [J].
BEVAN, AP ;
BURGESS, JW ;
DRAKE, PG ;
SHAVER, A ;
BERGERON, JJM ;
POSNER, BI .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (18) :10784-10791
[8]   TRANSFERRIN RECEPTOR AND ITS RECYCLING IN HELA-CELLS [J].
BLEIL, JD ;
BRETSCHER, MS .
EMBO JOURNAL, 1982, 1 (03) :351-355
[9]   THE CYTOPLASMIC DOMAIN MEDIATES LOCALIZATION OF FURIN TO THE TRANS-GOLGI NETWORK EN-ROUTE TO THE ENDOSOMAL LYSOSOMAL SYSTEM [J].
BOSSHART, H ;
HUMPHREY, J ;
DEIGNAN, E ;
DAVIDSON, J ;
DRAZBA, J ;
YUAN, L ;
OORSCHOT, V ;
PETERS, PJ ;
BONIFACINO, JS .
JOURNAL OF CELL BIOLOGY, 1994, 126 (05) :1157-1172
[10]   Interaction of the cytoplasmic tail of CTLA-4 (CD152) with a clathrin-associated protein is negatively regulated by tyrosine phosphorylation [J].
Bradshaw, JD ;
Lu, P ;
Leytze, G ;
Rodgers, J ;
Schieven, GL ;
Bennett, KL ;
Linsley, PS ;
Kurtz, SE .
BIOCHEMISTRY, 1997, 36 (50) :15975-15982