| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115
To study the mechanism by which protein tyrosine phosphatases
(PTPs) regulate CD3-induced tyrosine phosphorylation, we investigated
the distribution of PTPs in subdomains of plasma membrane. We report
here that the bulk PTP activity associated with T cell membrane is
present outside the lipid rafts, as determined by sucrose density
gradient sedimentation. In Jurkat T cells, 
5–10% of Src homology 2
domain-containing tyrosine phosphatase (SHP-1) is constitutively
associated with plasma membrane, and nearly 50% of SHP-2 is
translocated to plasma membrane after vanadate treatment. Similar to
transmembrane PTP, CD45, the membrane-associated populations of SHP-1
and SHP-2 are essentially excluded from lipid rafts, where other
signaling molecules such as Lck, linker for activation of T cells, and
CD3
are enriched. We further demonstrated that CD3-induced tyrosine
phosphorylation of these substrates is largely restricted to lipid
rafts, unless PTPs are inhibited. It suggests that a restricted
partition of PTPs among membrane subdomains may regulate protein
tyrosine phosphorylation in T cell membrane. To test this hypothesis,
we targeted SHP-1 into lipid rafts by using the N-terminal region of
Lck (residues 1–14). The results indicate that the expression of
Lck/SHP-1 chimera inside lipid rafts profoundly inhibits CD3-induced
tyrosine phosphorylation of CD3/
, IL-2 generation, and nuclear
mobilization of NF-AT. Collectively, these results suggest that the
exclusion of PTPs from lipid rafts may be a mechanism that potentiates
TCR/CD3 activation.
This article has been cited by other articles:
|
|
 |
|
  Z. Chen, L. Chen, S.-W. Qiao, T. Nagaishi, and R. S. Blumberg Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 Inhibits Proximal TCR Signaling by Targeting ZAP-70 J. Immunol., May 1, 2008; 180(9): 6085 - 6093. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M. Adam, N. K. Mukhopadhyay, J. Kim, D. Di Vizio, B. Cinar, K. Boucher, K. R. Solomon, and M. R. Freeman Cholesterol Sensitivity of Endogenous and Myristoylated Akt Cancer Res., July 1, 2007; 67(13): 6238 - 6246. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Sankarshanan, Z. Ma, T. Iype, and U. Lorenz Identification of a Novel Lipid Raft-Targeting Motif in Src Homology 2-Containing Phosphatase 1 J. Immunol., July 1, 2007; 179(1): 483 - 490. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Y. Kim, S. J. Park, E.-h. Joe, and I. Jou Raft-mediated Src Homology 2 Domain-containing Proteintyrosine Phosphatase 2 (SHP-2) Regulation in Microglia J. Biol. Chem., April 28, 2006; 281(17): 11872 - 11878. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Matallanas, V. Sanz-Moreno, I. Arozarena, F. Calvo, L. Agudo-Ibanez, E. Santos, M. T. Berciano, and P. Crespo Distinct Utilization of Effectors and Biological Outcomes Resulting from Site-Specific Ras Activation: Ras Functions in Lipid Rafts and Golgi Complex Are Dispensable for Proliferation and Transformation Mol. Cell. Biol., January 1, 2006; 26(1): 100 - 116. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Xiao, H. Nishimoto, H. Hong, J. Kitaura, S. Nunomura, M. Maeda-Yamamoto, Y. Kawakami, C. A. Lowell, C. Ra, and T. Kawakami Positive and Negative Regulation of Mast Cell Activation by Lyn via the Fc{epsilon}RI J. Immunol., November 15, 2005; 175(10): 6885 - 6892. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. C. J. Fawcett and U. Lorenz Localization of Src Homology 2 Domain-Containing Phosphatase 1 (SHP-1) to Lipid Rafts in T Lymphocytes: Functional Implications and a Role for the SHP-1 Carboxyl Terminus J. Immunol., March 1, 2005; 174(5): 2849 - 2859. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Young, X. Zheng, D. Holowka, and B. Baird Reconstitution of Regulated Phosphorylation of Fc{epsilon}RI by a Lipid Raft-excluded Protein-tyrosine Phosphatase J. Biol. Chem., January 14, 2005; 280(2): 1230 - 1235. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. M. Vyas, H. Maniar, C. E. Lyddane, M. Sadelain, and B. Dupont Ligand Binding to Inhibitory Killer Cell Ig-Like Receptors Induce Colocalization with Src Homology Domain 2-Containing Protein Tyrosine Phosphatase 1 and Interruption of Ongoing Activation Signals J. Immunol., August 1, 2004; 173(3): 1571 - 1578. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Y. Kim, E. J. Park, E.-h. Joe, and I. Jou Curcumin Suppresses Janus Kinase-STAT Inflammatory Signaling through Activation of Src Homology 2 Domain-Containing Tyrosine Phosphatase 2 in Brain Microglia J. Immunol., December 1, 2003; 171(11): 6072 - 6079. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. E. Kilgore, J. D. Carter, U. Lorenz, and B. D. Evavold Cutting Edge: Dependence of TCR Antagonism on Src Homology 2 Domain-Containing Protein Tyrosine Phosphatase Activity J. Immunol., May 15, 2003; 170(10): 4891 - 4895. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-i. Yusa and K. S. Campbell Src Homology Region 2-Containing Protein Tyrosine Phosphatase-2 (SHP-2) Can Play a Direct Role in the Inhibitory Function of Killer Cell Ig-Like Receptors in Human NK Cells J. Immunol., May 1, 2003; 170(9): 4539 - 4547. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Z. Fernandis, R. P. Cherla, and R. K. Ganju Differential Regulation of CXCR4-mediated T-cell Chemotaxis and Mitogen-activated Protein Kinase Activation by the Membrane Tyrosine Phosphatase, CD45 J. Biol. Chem., March 7, 2003; 278(11): 9536 - 9543. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Fragoso, D. Ren, X. Zhang, M. W.-C. Su, S. J. Burakoff, and Y.-J. Jin Lipid Raft Distribution of CD4 Depends on its Palmitoylation and Association with Lck, and Evidence for CD4-Induced Lipid Raft Aggregation as an Additional Mechanism to Enhance CD3 Signaling J. Immunol., January 15, 2003; 170(2): 913 - 921. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Ostrovidov, L. M. Howard, M. Ikeda, A. Ikeda, and C. Waltenbaugh Restoration of ethanol-compromised Th1 responses by sodium orthovanadate Int. Immunol., November 1, 2002; 14(11): 1239 - 1245. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Guerra, F. Michel, A. Gati, C. Gaudin, Z. Mishal, B. Escudier, O. Acuto, S. Chouaib, and A. Caignard Engagement of the inhibitory receptor CD158a interrupts TCR signaling, preventing dynamic membrane reorganization in CTL/tumor cell interaction Blood, September 26, 2002; 100(8): 2874 - 2881. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Guntermann and D. R. Alexander CTLA-4 Suppresses Proximal TCR Signaling in Resting Human CD4+ T Cells by Inhibiting ZAP-70 Tyr319 Phosphorylation: A Potential Role for Tyrosine Phosphatases J. Immunol., May 1, 2002; 168(9): 4420 - 4429. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Alonso and J. Millan The role of lipid rafts in signalling and membrane trafficking in T lymphocytes J. Cell Sci., March 13, 2002; 114(22): 3957 - 3965. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Y. Hawash, K. P. Kesavan, A. I. Magee, R. L. Geahlen, and M. L. Harrison The Lck SH3 Domain Negatively Regulates Localization to Lipid Rafts through an Interaction with c-Cbl J. Biol. Chem., February 8, 2002; 277(7): 5683 - 5691. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. M. Vyas, K. M. Mehta, M. Morgan, H. Maniar, L. Butros, S. Jung, J. K. Burkhardt, and B. Dupont Spatial Organization of Signal Transduction Molecules in the NK Cell Immune Synapses During MHC Class I-Regulated Noncytolytic and Cytolytic Interactions J. Immunol., October 15, 2001; 167(8): 4358 - 4367. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
