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Association of the adaptor molecule LAT with CD4 and CD8 coreceptors identifies a new coreceptor function in T cell receptor signal transduction.

Publication ,  Journal Article
Bosselut, R; Zhang, W; Ashe, JM; Kopacz, JL; Samelson, LE; Singer, A
Published in: J Exp Med
November 15, 1999

Linker for activation of T cells (LAT) is an adaptor protein whose tyrosine phosphorylation is critical for transduction of the T cell receptor (TCR) signal. LAT phosphorylation is accomplished by the protein tyrosine kinase ZAP-70, but it is not at all clear how LAT (which is not associated with the TCR) encounters ZAP-70 (which is bound to the TCR). Here we show that LAT associates with surface CD4 and CD8 coreceptors and that its association is promoted by the same coreceptor cysteine motif that mediates Lck binding. In fact, LAT competes with Lck for binding to individual coreceptor molecules but differs from Lck in its preferential association with CD8 rather than CD4 in CD4(+)CD8(+) thymocytes. Importantly, as a consequence of LAT association with surface coreceptors, coengagement of the TCR with surface coreceptors induces LAT phosphorylation and the specific recruitment of downstream signaling mediators to coreceptor-associated LAT molecules. These results point to a new function for CD4 and CD8 coreceptors in TCR signal transduction, namely to promote LAT phosphorylation by ZAP-70 by recruiting LAT to major histocompatibility complex-engaged TCR complexes.

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Published In

J Exp Med

DOI

ISSN

0022-1007

Publication Date

November 15, 1999

Volume

190

Issue

10

Start / End Page

1517 / 1526

Location

United States

Related Subject Headings

  • src Homology Domains
  • Signal Transduction
  • Receptors, Antigen, T-Cell
  • Phosphorylation
  • Phosphoproteins
  • Mice, Inbred C57BL
  • Mice
  • Membrane Proteins
  • Immunology
  • Carrier Proteins
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Bosselut, R., Zhang, W., Ashe, J. M., Kopacz, J. L., Samelson, L. E., & Singer, A. (1999). Association of the adaptor molecule LAT with CD4 and CD8 coreceptors identifies a new coreceptor function in T cell receptor signal transduction. J Exp Med, 190(10), 1517–1526. https://doi.org/10.1084/jem.190.10.1517
Bosselut, R., W. Zhang, J. M. Ashe, J. L. Kopacz, L. E. Samelson, and A. Singer. “Association of the adaptor molecule LAT with CD4 and CD8 coreceptors identifies a new coreceptor function in T cell receptor signal transduction.J Exp Med 190, no. 10 (November 15, 1999): 1517–26. https://doi.org/10.1084/jem.190.10.1517.
Bosselut R, Zhang W, Ashe JM, Kopacz JL, Samelson LE, Singer A. Association of the adaptor molecule LAT with CD4 and CD8 coreceptors identifies a new coreceptor function in T cell receptor signal transduction. J Exp Med. 1999 Nov 15;190(10):1517–26.
Bosselut, R., et al. “Association of the adaptor molecule LAT with CD4 and CD8 coreceptors identifies a new coreceptor function in T cell receptor signal transduction.J Exp Med, vol. 190, no. 10, Nov. 1999, pp. 1517–26. Pubmed, doi:10.1084/jem.190.10.1517.
Bosselut R, Zhang W, Ashe JM, Kopacz JL, Samelson LE, Singer A. Association of the adaptor molecule LAT with CD4 and CD8 coreceptors identifies a new coreceptor function in T cell receptor signal transduction. J Exp Med. 1999 Nov 15;190(10):1517–1526.

Published In

J Exp Med

DOI

ISSN

0022-1007

Publication Date

November 15, 1999

Volume

190

Issue

10

Start / End Page

1517 / 1526

Location

United States

Related Subject Headings

  • src Homology Domains
  • Signal Transduction
  • Receptors, Antigen, T-Cell
  • Phosphorylation
  • Phosphoproteins
  • Mice, Inbred C57BL
  • Mice
  • Membrane Proteins
  • Immunology
  • Carrier Proteins