論文 - 詳細
| RRC ID | 72361 |
|---|---|
| 著者 | Henshall TL, Jones KL, Wilkinson R, Jackson DE. |
| タイトル | Src homology 2 domain-containing protein-tyrosine phosphatases, SHP-1 and SHP-2, are required for platelet endothelial cell adhesion molecule-1/CD31-mediated inhibitory signaling. |
| ジャーナル | J Immunol |
| Abstract |
Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) is a newly assigned member of the Ig immunoreceptor tyrosine-based inhibitory motif superfamily, and its functional role is suggested to be an inhibitory receptor that modulates immunoreceptor tyrosine-based activation motif-dependent signaling cascades. To test whether PECAM-1 is capable of delivering inhibitory signals in B cells and the functional requirement of protein-tyrosine phosphatases (PTPs) for this inhibitory signaling, we generated chimeric Fc gamma RIIB1-PECAM-1 receptors containing the extracellular and transmembrane portions of murine Fc gamma RIIB1 and the cytoplasmic domain of human PECAM-1. These chimeric receptors were stably expressed in chicken DT40 B cells either as wild-type or mutant cells deficient in SHP-1(-/-), SHP-2(-/-), SHIP(-/-), or SHP-1/2(-/-) and then assessed for their ability to inhibit B cell Ag receptor (BCR) signaling. Coligation of wild-type Fc gamma RIIB1-PECAM-1 with BCR resulted in inhibition of intracellular calcium release, suggesting that the cytoplasmic domain of PECAM-1 is capable of delivering an inhibitory signal that blocks BCR-mediated activation. This PECAM-1-mediated inhibitory signaling correlated with tyrosine phosphorylation of the Fc gamma RIIB1-PECAM-1 chimera, recruitment of SHP-1 and SHP-2 PTPs by the phosphorylated chimera, and attenuation of calcium mobilization responses. Mutational analysis of the two tyrosine residues, 663 and 686, constituting the immunoreceptor tyrosine-based inhibitory motifs in PECAM-1 revealed that both tyrosine residues play a crucial role in the inhibitory signal. Functional analysis of various PTP-deficient DT40 B cell lines stably expressing wild-type chimeric Fc gamma RIIB1-PECAM-1 receptor indicated that cytoplasmic Src homology 2-domain-containing phosphatases, SHP-1 and SHP-2, were both necessary and sufficient to deliver inhibitory negative regulation upon coligation of BCR complex with inhibitory receptor. |
| 巻・号 | 166(5) |
| ページ | 3098-106 |
| 公開日 | 2001-3-1 |
| DOI | 10.4049/jimmunol.166.5.3098 |
| PMID | 11207261 |
| MeSH | Amino Acid Motifs / genetics Amino Acid Motifs / immunology Animals B-Lymphocytes / enzymology* B-Lymphocytes / immunology* B-Lymphocytes / metabolism Cell Line Chickens Consensus Sequence / genetics Consensus Sequence / immunology Cytoplasm / immunology Down-Regulation / genetics Down-Regulation / immunology* Humans Intracellular Signaling Peptides and Proteins Lymphocyte Activation / genetics Mice Platelet Endothelial Cell Adhesion Molecule-1 / genetics Platelet Endothelial Cell Adhesion Molecule-1 / physiology* Protein Structure, Tertiary / genetics Protein Tyrosine Phosphatase, Non-Receptor Type 11 Protein Tyrosine Phosphatase, Non-Receptor Type 6 Protein Tyrosine Phosphatases / deficiency Protein Tyrosine Phosphatases / genetics Protein Tyrosine Phosphatases / physiology* Receptors, IgG / genetics Recombinant Fusion Proteins / immunology Recombinant Fusion Proteins / pharmacology SH2 Domain-Containing Protein Tyrosine Phosphatases Signal Transduction / genetics Signal Transduction / immunology* Tyrosine / genetics Tyrosine / physiology src Homology Domains / genetics src Homology Domains / immunology* |
| IF | 4.886 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 各媒体での言及数の合計 | 0 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | SHP1^(-) DT40(RCB1466) SHP1^(-)/SHP2^(-) DT40(RCB1501) SHP2^(-) DT40(RCB1502) SHIP^(-) DT40(RCB1465) |