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The importance of Src homology 2 domain-containing leukocyte phosphoprotein of 76 kilodaltons sterile-alpha motif domain in thymic selection and T-cell activation.

Publication ,  Journal Article
Shen, S; Lau, J; Zhu, M; Zou, J; Fuller, D; Li, Q-J; Zhang, W
Published in: Blood
July 2, 2009

The Src homology 2 domain-containing leukocyte phosphoprotein of 76 kilodaltons (SLP-76) is a cytosolic adaptor protein essential for thymocyte development and T-cell activation. It contains a sterile-alpha motif (SAM) domain, 3 phosphotyrosine motifs, a proline-rich region, and a Src homology 2 domain. Whereas the other domains have been extensively studied, the role of the SAM domain in SLP-76 function is not known. To understand the function of this domain, we generated SLP-76 knockin mice with the SAM domain deleted. Analysis of these mice showed that thymocyte development was partially blocked at the double-positive to single-positive transition. Positive and negative thymic selection was also impaired. In addition, we analyzed T-cell receptor (TCR)-mediated signaling in T cells from these mutant mice. TCR-mediated inositol 1,4,5-triphosphate production, calcium flux, and extracellular signal-regulated kinase activation were decreased, leading to defective interleukin-2 production and proliferation. Moreover, despite normal association between Gads and SLP-76, TCR-mediated formation of SLP-76 microclusters was impaired by the deletion of the SAM domain. Altogether, our data demonstrated that the SAM domain is indispensable for optimal SLP-76 signaling.

Duke Scholars

Published In

Blood

DOI

EISSN

1528-0020

Publication Date

July 2, 2009

Volume

114

Issue

1

Start / End Page

74 / 84

Location

United States

Related Subject Headings

  • Thymus Gland
  • T-Lymphocytes
  • Signal Transduction
  • Sequence Deletion
  • Recombinant Proteins
  • Receptors, Antigen, T-Cell
  • Protein Structure, Tertiary
  • Phosphoproteins
  • Mice, Transgenic
  • Mice, Mutant Strains
 

Citation

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Shen, S., Lau, J., Zhu, M., Zou, J., Fuller, D., Li, Q.-J., & Zhang, W. (2009). The importance of Src homology 2 domain-containing leukocyte phosphoprotein of 76 kilodaltons sterile-alpha motif domain in thymic selection and T-cell activation. Blood, 114(1), 74–84. https://doi.org/10.1182/blood-2008-09-177832
Shen, Shudan, Jasmine Lau, Minghua Zhu, Jianwei Zou, Deirdre Fuller, Qi-jing Li, and Weiguo Zhang. “The importance of Src homology 2 domain-containing leukocyte phosphoprotein of 76 kilodaltons sterile-alpha motif domain in thymic selection and T-cell activation.Blood 114, no. 1 (July 2, 2009): 74–84. https://doi.org/10.1182/blood-2008-09-177832.
Shen, Shudan, et al. “The importance of Src homology 2 domain-containing leukocyte phosphoprotein of 76 kilodaltons sterile-alpha motif domain in thymic selection and T-cell activation.Blood, vol. 114, no. 1, July 2009, pp. 74–84. Pubmed, doi:10.1182/blood-2008-09-177832.

Published In

Blood

DOI

EISSN

1528-0020

Publication Date

July 2, 2009

Volume

114

Issue

1

Start / End Page

74 / 84

Location

United States

Related Subject Headings

  • Thymus Gland
  • T-Lymphocytes
  • Signal Transduction
  • Sequence Deletion
  • Recombinant Proteins
  • Receptors, Antigen, T-Cell
  • Protein Structure, Tertiary
  • Phosphoproteins
  • Mice, Transgenic
  • Mice, Mutant Strains