![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
|
|
|
|
|
||
A more recent version of this article appeared on June 1, 2004
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on September 9, 2003
Revised on March 23, 2004
Accepted on March 26, 2004
1 Department of Biochemistry, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021
* Corresponding author. E-mail address: frmaxfie{at}med.cornell.edu.
Furin is a transmembrane protein that cycles between the plasma membrane, endosomes, and the trans-Golgi network, maintaining a predominant distribution in the latter. It has been shown previously that Tac-furin, a chimeric protein expressing the extracellular and transmembrane domains of the interleukin-2 receptor 
chain (Tac) and the cytoplasmic domain of furin, is delivered from the plasma membrane to the TGN through late endosomes, bypassing the endocytic recycling compartment. Tac-furin also recycles in a loop between the TGN and late endosomes. Localization of furin to the TGN is modulated by a six-amino acid acidic cluster that contains two phosphorylatable serines (SDSEED). We investigated the role of these serines in the trafficking of Tac-furin using a mutant chimera in which the SDS sequence was replaced by the nonphosphorylatable sequence ADA (Tac-furin/ADA). While the mutant construct is internalized and delivered to the TGN, both the postendocytic trafficking and the steady state distribution were found to differ from the wild-type. In contrast with Tac-furin, Tac-furin/ADA does not enter late endosomes after being internalized. Instead, it traffics with transferrin to the endocytic recycling compartment, and from there it is delivered to the TGN. As with Tac-furin, Tac-furin/ADA is sorted from the TGN into late endosomes at steady state, but its retrieval from the late endosomes to the TGN is inhibited. These results suggest that serine phosphorylation plays an important role in at least two steps of Tac-furin trafficking, acting as an active sorting signal that mediates the selective sorting of Tac-furin into late endosomes after internalization, as well as its retrieval from late endosomes back to the TGN.
This article has been cited by other articles:
|
|
 |
|
  L. L. Baugh, J. V. Garcia, and J. L. Foster Functional Characterization of the Human Immunodeficiency Virus Type 1 Nef Acidic Domain J. Virol., October 1, 2008; 82(19): 9657 - 9667. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Han, Y. Wang, S. Wang, and C. Chi Interaction of Mint3 with Furin regulates the localization of Furin in the trans-Golgi network J. Cell Sci., July 1, 2008; 121(13): 2217 - 2223. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Ishizaki, H.-W. Shin, H. Mitsuhashi, and K. Nakayama Redundant Roles of BIG2 and BIG1, Guanine-Nucleotide Exchange Factors for ADP-Ribosylation Factors in Membrane Traffic between the trans-Golgi Network and Endosomes Mol. Biol. Cell, June 1, 2008; 19(6): 2650 - 2660. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Lecuona, L. A. Dada, H. Sun, M. L. Butti, G. Zhou, T.-L. Chew, and J. I. Sznajder Na,K-ATPase {alpha}1-subunit dephosphorylation by protein phosphatase 2A is necessary for its recruitment to the plasma membrane FASEB J, December 1, 2006; 20(14): 2618 - 2620. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Loomis, R. J. Courtney, and J. W. Wills Packaging Determinants in the UL11 Tegument Protein of Herpes Simplex Virus Type 1 J. Virol., November 1, 2006; 80(21): 10534 - 10541. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Zhu, K. Liu, J. Cerny, T. Imoto, and K. D. Moudgil Insertion of the Dibasic Motif in the Flanking Region of a Cryptic Self-Determinant Leads to Activation of the Epitope-Specific T Cells J. Immunol., August 15, 2005; 175(4): 2252 - 2260. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. D. Austin, A. M. De Maziere, P. I. Pisacane, S. M. van Dijk, C. Eigenbrot, M. X. Sliwkowski, J. Klumperman, and R. H. Scheller Endocytosis and Sorting of ErbB2 and the Site of Action of Cancer Therapeutics Trastuzumab and Geldanamycin Mol. Biol. Cell, December 1, 2004; 15(12): 5268 - 5282. [Abstract] [Full Text] [PDF]
|
|
