G6b, a novel immunoglobulin superfamily member encoded in the human major histocompatibility complex, interacts with SHP-1 and SHP-2

被引:44
作者
de Vet, ECJM [1 ]
Aguado, B [1 ]
Campbell, RD [1 ]
机构
[1] MRC UK HGMP Resource Ctr, Cambridge CB10 1SB, England
关键词
D O I
10.1074/jbc.M103214200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The G6b gene, located in the class III region of the human major histocompatibility complex, has been suggested to encode a putative receptor of the immunoglobulin superfamily. Genomic sequence information was used as a starting point to clone the corresponding cDNA. Reverse transcriptase polymerase chain reaction showed that expression of the gene is restricted to certain hematopoietic cell lines including K562, Molt 4, and Jurkat. Several splice variants were detected, varying only in their C-terminal parts. One of the potential membrane-bound isoforms contained two immunoreceptor tyrosine-based inhibitory motifs in its cytoplasmic tail. Four of the isoforms were expressed as epitope-tagged proteins in the cell lines K562 and COS-7. The two splice isoforms lacking the hydrophobic transmembrane segment were secreted from the cell. Glycosidase treatment of the four recombinant proteins provided evidence for N- and O-glycosylation. Immunofluorescence studies indicated that the spliced isoforms having a transmembrane segment were directed to the cell membrane. The G6b isoform containing two immunoreceptor tyrosine-based inhibitory motifs in its cytoplasmic tail was found to be phosphorylated on tyrosine residues after pervanadate treatment of cells and, subsequently, interacts with the SH2-containing protein-tyrosine phosphatases SHP-1 and SHP-2. Mutagenesis studies showed that phosphorylation of tyrosine 211 is critical for the interaction of G6b with SHP-1 and SHP-2.
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页码:42070 / 42076
页数:7
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