| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02115; and Departments of
Pathology,
Medicine, and
§
Dental Medicine, Harvard Medical School, Boston, MA 02115
Although the lipid kinase phosphatidylinositol 3-kinase (PI-3K)
binds at high levels to the cytoplasmic tail of CD28, controversy
exists regarding its role in CD28 costimulation. Potentially, the
kinase could be linked to a signaling cascade or be needed indirectly
in events such as receptor endocytosis. Indeed, little is known
regarding both the fate of CD28 following receptor ligation and the
events that control the process. In this study, we help to resolve this
issue by providing evidence that PI-3K plays a role in regulating CD28
endocytosis. We show that 
25 to 35% of wild-type CD28 becomes
endocytosed following Ab binding (t1/2 =
10 min), followed by segregation into two pools; one pool is destined
for degradation in lysosomal compartments and is blocked by
chloroquine, and another pool that is recycled to the cell surface
(t1/2 = 2.5 h). Recycling of CD28
could have an important impact on CD80/86-mediated costimulation by
replenishing functionally active receptors on the cell surface. Several
findings implicate PI-3K in the control of endocytosis. Modulation
experiments indicate that CD28-PI-3K complexes are preferentially
endocytosed, and mutations that alter PI-3K binding concordantly affect
the efficacy of endocytosis. Importantly, mutations that inhibit
receptor internalization also block cosignaling. Therefore, previous
results documenting a requirement for PI-3K may be explained by a
blockage of receptor internalization.
This article has been cited by other articles:
|
|
 |
|
  S. Aguera-Gonzalez, P. Boutet, H. T. Reyburn, and M. Vales-Gomez Brief Residence at the Plasma Membrane of the MHC Class I-Related Chain B Is Due to Clathrin-Mediated Cholesterol-Dependent Endocytosis and Shedding J. Immunol., April 15, 2009; 182(8): 4800 - 4808. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Berg and N. Zavazava Regulation of CD28 expression on CD8+ T cells by CTLA-4 J. Leukoc. Biol., April 1, 2008; 83(4): 853 - 863. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Badour, M. K. H. McGavin, J. Zhang, S. Freeman, C. Vieira, D. Filipp, M. Julius, G. B. Mills, and K. A. Siminovitch Interaction of the Wiskott-Aldrich syndrome protein with sorting nexin 9 is required for CD28 endocytosis and cosignaling in T cells PNAS, January 30, 2007; 104(5): 1593 - 1598. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Raghuraman, Y. Geng, and C.-R. Wang IFN-beta-Mediated Up-Regulation of CD1d in Bacteria-Infected APCs J. Immunol., December 1, 2006; 177(11): 7841 - 7848. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. P. Lawton, T. I. Prigozy, L. Brossay, B. Pei, A. Khurana, D. Martin, T. Zhu, K. Spate, M. Ozga, S. Honing, et al. The Mouse CD1d Cytoplasmic Tail Mediates CD1d Trafficking and Antigen Presentation by Adaptor Protein 3-Dependent and -Independent Mechanisms J. Immunol., March 15, 2005; 174(6): 3179 - 3186. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Sundberg, N. Beauchemin, and B. Obrink The cytoplasmic domain of CEACAM1-L controls its lateral localization and the organization of desmosomes in polarized epithelial cells J. Cell Sci., March 1, 2004; 117(7): 1091 - 1104. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Del Valle, P. Engel, and M. Martin The Cell Surface Expression of SAP-binding Receptor CD229 Is Regulated via Its Interaction with Clathrin-associated Adaptor Complex 2 (AP-2) J. Biol. Chem., May 2, 2003; 278(19): 17430 - 17437. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Yin, H. Schneider, and C. E. Rudd Short cytoplasmic SDYMNM segment of CD28 is sufficient to convert CTLA-4 to a positive signaling receptor J. Leukoc. Biol., January 1, 2003; 73(1): 178 - 182. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Lu, R. C. Axtell, J. F. Collawn, A. Gibson, L. B. Justement, and C. Raman AP2 Adaptor Complex-Dependent Internalization of CD5: Differential Regulation in T and B Cells J. Immunol., June 1, 2002; 168(11): 5612 - 5620. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. G. Drake, A. Balbis, J. Wu, J. J. M. Bergeron, and B. I. Posner Association of phosphatidylinositol 3-kinase with the insulin receptor: compartmentation in rat liver Am J Physiol Endocrinol Metab, August 1, 2000; 279(2): E266 - E274. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Oki, T. Kohsaka, and M. Azuma Augmentation of CTLA-4 expression by wortmannin: involvement of lysosomal sorting properties of CTLA-4 Int. Immunol., September 1, 1999; 11(9): 1563 - 1571. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Boulougouris, J. D. McLeod, Y. I. Patel, C. N. Ellwood, L. S. K. Walker, and D. M. Sansom IL-2-Independent Activation and Proliferation in Human T Cells Induced by CD28 J. Immunol., August 15, 1999; 163(4): 1809 - 1816. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Olsson, K. Riebeck, M. Dohlsten, and E. Michaelsson CTLA-4 Ligation Suppresses CD28-induced NF-kappa B and AP-1 Activity in Mouse T Cell Blasts J. Biol. Chem., May 14, 1999; 274(20): 14400 - 14405. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Metzler, C. Burkhart, and D. C. Wraith Phenotypic analysis of CTLA-4 and CD28 expression during transient peptide-induced T cell activation in vivo Int. Immunol., May 1, 1999; 11(5): 667 - 675. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
