Cell surface receptors Ly-9 and CD84 recruit the X-linked lymphoproliferative disease gene product SAP

Blood. 2001 Jun 15;97(12):3867-74. doi: 10.1182/blood.v97.12.3867.


X-linked lymphoproliferative disease (XLP) is a rare immune disorder commonly triggered by infection with Epstein-Barr virus. Major disease manifestations include fatal acute infectious mononucleosis, B-cell lymphoma, and progressive dys-gammaglobulinemia. SAP/SH2D1A, the product of the gene mutated in XLP, is a small protein that comprises a single SH2 domain and a short tail of 26 amino acids. SAP binds to a specific motif in the cytoplasmic tails of the cell surface receptors SLAM and 2B4, where it blocks recruitment of the phosphatase SHP-2. Here it is reported that Ly-9 and CD84, 2 related glycoproteins differentially expressed on hematopoietic cells, also recruit SAP. Interactions between SAP and Ly-9 or CD84 were analyzed using a novel yeast 2-hybrid system, by COS cell transfections and in lymphoid cells. Recruitment of SAP is most efficient when the specific tyrosine residues in the cytoplasmic tails of Ly-9 or CD84 are phosphorylated. It is concluded that in activated T cells, the SAP protein binds to and regulates signal transduction events initiated through the engagement of SLAM, 2B4, CD84, and Ly-9. This suggests that combinations of dysfunctional signaling pathways initiated by these 4 cell surface receptors may cause the complex phenotypes of XLP. (Blood. 2001;97:3867-3874)

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigens, CD / genetics
  • Antigens, CD / pharmacology*
  • Antigens, CD / physiology
  • Binding Sites
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • Genetic Linkage
  • Humans
  • Intracellular Signaling Peptides and Proteins*
  • Jurkat Cells
  • Lymphoproliferative Disorders / genetics
  • Lymphoproliferative Disorders / metabolism
  • Membrane Glycoproteins*
  • Phosphorylation
  • Protein Binding
  • Receptor Aggregation
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / physiology
  • Signaling Lymphocytic Activation Molecule Associated Protein
  • Signaling Lymphocytic Activation Molecule Family
  • Transfection
  • Two-Hybrid System Techniques
  • X Chromosome


  • Antigens, CD
  • CD84 protein, human
  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • LY9 protein, human
  • Membrane Glycoproteins
  • Receptors, Cell Surface
  • SH2D1A protein, human
  • Signaling Lymphocytic Activation Molecule Associated Protein
  • Signaling Lymphocytic Activation Molecule Family