Identification and characterization of SF2000 and SF2001, two new members of the immune receptor SLAM/CD2 family.
The SLAM family of human genes currently consists of seven related members of the immunoglobulin superfamily, membrane-associated proteins, including CD150 (SLAM), CD244 (2B4), CD84, CD229 ( Ly-9), BLAME, CD48, and 19A. These genes are expressed to varying degrees in subsets of immune cells (T, B, natural killer, and myeloid cells) and may function as ligands or receptors. This set of genes, related to CD2 and CD58 on Chromosome (Chr) 1p98, are found clustered close together in the human genome on Chr 1q22. Four of these family members (CD150, CD244, CD84, CD229) contain conserved tyrosine motifs in their cytoplasmic tails that enable them to bind intracellular signaling molecules SAP and EAT-2. SAP is mutated in human X-linked lymphoproliferative disease (XLP), and studies in XLP patients have shown that improper signaling via molecules that bind SAP contributes to the disease. We have identified two new members of the SLAM family (SF), which we term SF2000 and SF2001, which are expressed in immune cells and map in the SLAM gene cluster. SF2001 does not contain SAP-binding motifs in its short cytoplasmic tail. SF2000, which is co-expressed with SAP in T cells, binds both SAP and EAT-2. The data suggest that signaling through SF2000, together with CD150, CD244, CD84, and CD229, is controlled by SAP and therefore contributes to the pathogenesis of XLP.
Fraser
Christopher C
CC
Millennium Pharmaceuticals, 75 Sidney Street, Cambridge, MA 02139, USA. fraser@mpi.com
Howie
Duncan
D
Morra
Massimo
M
Qiu
Yubin
Y
Murphy
Curran
C
Shen
Qiong
Q
Gutierrez-Ramos
Jose-Carlos
JC
Coyle
Anthony
A
Kingsbury
Gillian A
GA
Terhorst
Cox
C
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD; D018801:CD2 Antigens / Q000737:chemistry* / Q000235:genetics; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D020224:Expressed Sequence Tags; D020869:Gene Expression Profiling; D006023:Glycoproteins / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry* / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D008214:Lymphocytes / Q000378:metabolism; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D010802:Phylogeny; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051076:Proto-Oncogene Proteins c-fyn; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D000071176:Signaling Lymphocytic Activation Molecule Family; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D020798:Two-Hybrid System Techniques
D015703:Antigens, CD; D018801:CD2 Antigens; D002352:Carrier Proteins; D006023:Glycoproteins; D007136:Immunoglobulins; D047908:Intracellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C114953:SH2D1A protein, human; C000604059:SLAMF1 protein, human; C000604060:SLAMF6 protein, human; C000604061:SLAMF9 protein, human; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D000071176:Signaling Lymphocytic Activation Molecule Family; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D019000:Phosphotyrosine; C494957:FYN protein, human; D051076:Proto-Oncogene Proteins c-fyn