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Protein interactions between CD2 and Lck are required for the lipid raft distribution of CD2

Nunes, Raquel J.; Castro, Mónica A.A.; Gonçalves, Carine M.; Bamberger, Martina; Pereira, Carlos F. LU ; Bismuth, Georges and Carmo, Alexandre M. (2008) In Journal of Immunology 180(2). p.988-997
Abstract

In T lymphocytes, lipid rafts are preferred sites for signal transduction initiation and amplification. Many cell membrane receptors, such as the TCR, coreceptors, and accessory molecules associate within these microdomains upon cell activation. However, it is still unclear in most cases whether these receptors interact with rafts through lipid-based amino acid modifications or whether raft insertion is driven by protein-protein interactions. In murine T cells, a significant fraction of CD2 associates with membrane lipid rafts. We have addressed the mechanisms that control the localization of rat CD2 at the plasma membrane, and its redistribution within lipid rafts induced upon activation. Following incubation of rat CD2-expressing... (More)

In T lymphocytes, lipid rafts are preferred sites for signal transduction initiation and amplification. Many cell membrane receptors, such as the TCR, coreceptors, and accessory molecules associate within these microdomains upon cell activation. However, it is still unclear in most cases whether these receptors interact with rafts through lipid-based amino acid modifications or whether raft insertion is driven by protein-protein interactions. In murine T cells, a significant fraction of CD2 associates with membrane lipid rafts. We have addressed the mechanisms that control the localization of rat CD2 at the plasma membrane, and its redistribution within lipid rafts induced upon activation. Following incubation of rat CD2-expressing cells with radioactive-labeled palmitic acid, or using CD2 mutants with Cys226 and Cys228 replaced by alanine residues, we found no evidence that rat CD2 was subjected to lipid modifications that could favor the translocation to lipid rafts, discarding palmitoylation as the principal mechanism for raft addressing. In contrast, using Jurkat cells expressing different CD2 and Lck mutants, we show that the association of CD2 with the rafts fully correlates with CD2 capacity to bind to Lck. As CD2 physically interacts with both Lck and Fyn, preferentially inside lipid rafts, and reflecting the increase of CD2 in lipid rafts following activation, CD2 can mediate the interaction between the two kinases and the consequent boost in kinase activity in lipid rafts.

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author
publishing date
type
Contribution to journal
publication status
published
in
Journal of Immunology
volume
180
issue
2
pages
10 pages
publisher
American Association of Immunologists
external identifiers
  • scopus:40449133966
ISSN
0022-1767
DOI
10.4049/jimmunol.180.2.988
language
English
LU publication?
no
id
272eab00-5cd1-49b6-8743-e7e09e2eac55
date added to LUP
2017-10-02 17:32:47
date last changed
2017-10-13 08:55:26
@article{272eab00-5cd1-49b6-8743-e7e09e2eac55,
  abstract     = {<p>In T lymphocytes, lipid rafts are preferred sites for signal transduction initiation and amplification. Many cell membrane receptors, such as the TCR, coreceptors, and accessory molecules associate within these microdomains upon cell activation. However, it is still unclear in most cases whether these receptors interact with rafts through lipid-based amino acid modifications or whether raft insertion is driven by protein-protein interactions. In murine T cells, a significant fraction of CD2 associates with membrane lipid rafts. We have addressed the mechanisms that control the localization of rat CD2 at the plasma membrane, and its redistribution within lipid rafts induced upon activation. Following incubation of rat CD2-expressing cells with radioactive-labeled palmitic acid, or using CD2 mutants with Cys<sup>226</sup> and Cys<sup>228</sup> replaced by alanine residues, we found no evidence that rat CD2 was subjected to lipid modifications that could favor the translocation to lipid rafts, discarding palmitoylation as the principal mechanism for raft addressing. In contrast, using Jurkat cells expressing different CD2 and Lck mutants, we show that the association of CD2 with the rafts fully correlates with CD2 capacity to bind to Lck. As CD2 physically interacts with both Lck and Fyn, preferentially inside lipid rafts, and reflecting the increase of CD2 in lipid rafts following activation, CD2 can mediate the interaction between the two kinases and the consequent boost in kinase activity in lipid rafts.</p>},
  author       = {Nunes, Raquel J. and Castro, Mónica A.A. and Gonçalves, Carine M. and Bamberger, Martina and Pereira, Carlos F. and Bismuth, Georges and Carmo, Alexandre M.},
  issn         = {0022-1767},
  language     = {eng},
  month        = {01},
  number       = {2},
  pages        = {988--997},
  publisher    = {American Association of Immunologists},
  series       = {Journal of Immunology},
  title        = {Protein interactions between CD2 and Lck are required for the lipid raft distribution of CD2},
  url          = {http://dx.doi.org/10.4049/jimmunol.180.2.988},
  volume       = {180},
  year         = {2008},
}