![[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}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 17, Issue 2, 645-657, February 2006
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
* Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104;
Department of Pathology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104; and
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198
Submitted July 21, 2005;
Revised October 26, 2005;
Accepted November 14, 2005
Monitoring Editor: Sandra Schmid
Extracellular signal-regulated kinase (Erk) is widely recognized for its central role in cell proliferation and motility. Although previous work has shown that Erk is localized at endosomal compartments, no role for Erk in regulating endosomal trafficking has been demonstrated. Here, we report that Erk signaling regulates trafficking through the clathrin-independent, ADP-ribosylation factor 6 (Arf6) GTPase-regulated endosomal pathway. Inactivation of Erk induced by a variety of methods leads to a dramatic expansion of the Arf6 endosomal recycling compartment, and intracellular accumulation of cargo, such as class I major histocompatibility complex, within the expanded endosome. Treatment of cells with the mitogen-activated protein kinase kinase (MEK) inhibitor U0126 reduces surface expression of MHCI without affecting its rate of endocytosis, suggesting that inactivation of Erk perturbs recycling. Furthermore, under conditions where Erk activity is inhibited, a large cohort of Erk, MEK, and the Erk scaffold kinase suppressor of Ras 1 accumulates at the Arf6 recycling compartment. The requirement for Erk was highly specific for this endocytic pathway, because its inhibition had no effect on trafficking of cargo of the classical clathrin-dependent pathway. These studies reveal a previously unappreciated link of Erk signaling to organelle dynamics and endosomal trafficking.
Abbreviations used: Arf6, ADP-ribosylation factor 6; Erk, extracellular signal-regulated kinase; KSR, kinase suppressor of Ras; MHCI, class I major histocompatibility complex.
The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).
Address correspondence to: Margaret M. Chou (mmc{at}mail.med.upenn.edu).
This article has been cited by other articles:
|
|
 |
|
  D. Marchant, A. Sall, X. Si, T. Abraham, W. Wu, Z. Luo, T. Petersen, R. G. Hegele, and B. M. McManus ERK MAP kinase-activated Arf6 trafficking directs coxsackievirus type B3 into an unproductive compartment during virus host-cell entry J. Gen. Virol., April 1, 2009; 90(4): 854 - 862. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. A. Moser and S. Schultz-Cherry Suppression of Astrovirus Replication by an ERK1/2 Inhibitor J. Virol., August 1, 2008; 82(15): 7475 - 7482. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Porat-Shliom, Y. Kloog, and J. G. Donaldson A Unique Platform for H-Ras Signaling Involving Clathrin-independent Endocytosis Mol. Biol. Cell, March 1, 2008; 19(3): 765 - 775. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Moskovich and Z. Fishelson Live Cell Imaging of Outward and Inward Vesiculation Induced by the Complement C5b-9 Complex J. Biol. Chem., October 12, 2007; 282(41): 29977 - 29986. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Tolg, S. R. Hamilton, K.-A. Nakrieko, F. Kooshesh, P. Walton, J. B. McCarthy, M. J. Bissell, and E. A. Turley Rhamm-/- fibroblasts are defective in CD44-mediated ERK1,2 motogenic signaling, leading to defective skin wound repair J. Cell Biol., December 18, 2006; 175(6): 1017 - 1028. [Abstract] [Full Text] [PDF]
|
|
