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Distinct interactions of the X-linked lymphoproliferative syndrome gene product SAP with cytoplasmic domains of members of the CD2 receptor family.

Publication ,  Journal Article
Lewis, J; Eiben, LJ; Nelson, DL; Cohen, JI; Nichols, KE; Ochs, HD; Notarangelo, LD; Duckett, CS
Published in: Clin Immunol
July 2001

X-linked lymphoproliferative syndrome (XLP; Duncan's disease) is a primary immunodeficiency disease that manifests as an inability to regulate the immune response to Epstein-Barr virus (EBV) infection. Here we examine the ability of the product of the gene defective in XLP, SAP (DSHP/SH2D1A), to associate with the cytoplasmic domains of several members of the CD2 subfamily of cell surface receptors, including SLAM, 2B4, and CD84. While recruitment of SAP to SLAM occurred in a phosphorylation-independent manner, SAP was found to bind preferentially to tyrosine-phosphorylated cytoplasmic domains within 2B4 and CD84. Missense or nonsense mutations in the SAP open reading frame were identified in five of seven clinically diagnosed XLP patients from different kindreds. Four of these variants retained the ability to bind to the cytoplasmic tails of SLAM and CD84. While ectopic expression of wild-type SAP was observed to block the binding of SHP-2 to SLAM, mutant SAP derivatives that retained the ability to bind SLAM did not inhibit recruitment of SHP-2 to SLAM. In contrast, SAP binding to CD84 had no effect on the ability of CD84 to recruit SHP-2, but instead displaced SHP-1 from the cytoplasmic tail of CD84. These results suggest that mutations in the gene encoding the XLP protein SAP lead to functional defects in the protein that include receptor binding and SHP-1 and SHP-2 displacement and that SAP utilizes different mechanisms to regulate signaling through the CD2 family of receptors.

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Published In

Clin Immunol

DOI

ISSN

1521-6616

Publication Date

July 2001

Volume

100

Issue

1

Start / End Page

15 / 23

Location

United States

Related Subject Headings

  • src Homology Domains
  • Transfection
  • Signaling Lymphocytic Activation Molecule Family Member 1
  • Signaling Lymphocytic Activation Molecule Family
  • Signaling Lymphocytic Activation Molecule Associated Protein
  • Signal Transduction
  • SH2 Domain-Containing Protein Tyrosine Phosphatases
  • Recombinant Fusion Proteins
  • Receptors, Cell Surface
  • Protein Tyrosine Phosphatases
 

Citation

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Lewis, J., Eiben, L. J., Nelson, D. L., Cohen, J. I., Nichols, K. E., Ochs, H. D., … Duckett, C. S. (2001). Distinct interactions of the X-linked lymphoproliferative syndrome gene product SAP with cytoplasmic domains of members of the CD2 receptor family. Clin Immunol, 100(1), 15–23. https://doi.org/10.1006/clim.2001.5035
Lewis, J., L. J. Eiben, D. L. Nelson, J. I. Cohen, K. E. Nichols, H. D. Ochs, L. D. Notarangelo, and C. S. Duckett. “Distinct interactions of the X-linked lymphoproliferative syndrome gene product SAP with cytoplasmic domains of members of the CD2 receptor family.Clin Immunol 100, no. 1 (July 2001): 15–23. https://doi.org/10.1006/clim.2001.5035.
Lewis J, Eiben LJ, Nelson DL, Cohen JI, Nichols KE, Ochs HD, et al. Distinct interactions of the X-linked lymphoproliferative syndrome gene product SAP with cytoplasmic domains of members of the CD2 receptor family. Clin Immunol. 2001 Jul;100(1):15–23.
Lewis, J., et al. “Distinct interactions of the X-linked lymphoproliferative syndrome gene product SAP with cytoplasmic domains of members of the CD2 receptor family.Clin Immunol, vol. 100, no. 1, July 2001, pp. 15–23. Pubmed, doi:10.1006/clim.2001.5035.
Lewis J, Eiben LJ, Nelson DL, Cohen JI, Nichols KE, Ochs HD, Notarangelo LD, Duckett CS. Distinct interactions of the X-linked lymphoproliferative syndrome gene product SAP with cytoplasmic domains of members of the CD2 receptor family. Clin Immunol. 2001 Jul;100(1):15–23.
Journal cover image

Published In

Clin Immunol

DOI

ISSN

1521-6616

Publication Date

July 2001

Volume

100

Issue

1

Start / End Page

15 / 23

Location

United States

Related Subject Headings

  • src Homology Domains
  • Transfection
  • Signaling Lymphocytic Activation Molecule Family Member 1
  • Signaling Lymphocytic Activation Molecule Family
  • Signaling Lymphocytic Activation Molecule Associated Protein
  • Signal Transduction
  • SH2 Domain-Containing Protein Tyrosine Phosphatases
  • Recombinant Fusion Proteins
  • Receptors, Cell Surface
  • Protein Tyrosine Phosphatases