論文 - 詳細
| RRC ID | 72362 |
|---|---|
| 著者 | Newman DK, Hamilton C, Newman PJ. |
| タイトル | Inhibition of antigen-receptor signaling by Platelet Endothelial Cell Adhesion Molecule-1 (CD31) requires functional ITIMs, SHP-2, and p56(lck). |
| ジャーナル | Blood |
| Abstract |
Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1, CD31) is a 130-kd member of the immunoglobulin gene superfamily that is expressed on the surface of platelets, endothelial cells, myeloid cells, and certain lymphocyte subsets. PECAM-1 has recently been shown to contain functional immunoreceptor tyrosine-based inhibitory motifs (ITIMs) within its cytoplasmic domain, and co-ligation of PECAM-1 with the T-cell antigen receptor (TCR) results in tyrosine phosphorylation of PECAM-1, recruitment of Src homology 2 domain-containing protein tyrosine phosphatase-2 (SHP-2), and attenuation of TCR-mediated cellular signaling. To determine the molecular basis of PECAM-1 inhibitory signaling in lymphocytes, the study sought to (1) establish the importance of the PECAM-1 ITIMs for its inhibitory activity, (2) determine the relative importance of SHP-2 versus SHP-1 in mediating the inhibitory effect of PECAM-1, and (3) identify the protein tyrosine kinases required for PECAM-1 tyrosine phosphorylation in T cells. Co-ligation of wild-type PECAM-1 with the B-cell antigen receptor expressed on chicken DT40 B cells resulted in a marked reduction of calcium mobilization-similar to previous observations in T cells. In contrast, co-ligation of an ITIM-less form of PECAM-1 had no inhibitory effect. Furthermore, wild-type PECAM-1 was unable to attenuate calcium mobilization in SHP-2-deficient DT40 variants despite abundant levels of SHP-1 in these cells. Finally, PECAM-1 failed to become tyrosine phosphorylated in p56(lck)-deficient Jurkat T cells. Together, these data provide important insights into the molecular requirements for PECAM-1 regulation of antigen receptor signaling. |
| 巻・号 | 97(8) |
| ページ | 2351-7 |
| 公開日 | 2001-4-15 |
| DOI | 10.1182/blood.v97.8.2351 |
| PII | S0006-4971(20)55757-1 |
| PMID | 11290597 |
| MeSH | Amino Acid Motifs Animals Antibodies, Monoclonal / pharmacology CD3 Complex / immunology CD3 Complex / physiology Calcium Signaling / drug effects Calcium Signaling / physiology* Chickens Humans Intracellular Signaling Peptides and Proteins Jurkat Cells / drug effects Jurkat Cells / enzymology Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / deficiency Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / physiology* Phosphorylation Platelet Endothelial Cell Adhesion Molecule-1 / chemistry Platelet Endothelial Cell Adhesion Molecule-1 / genetics Platelet Endothelial Cell Adhesion Molecule-1 / physiology* Protein Phosphatase 2 Protein Processing, Post-Translational Protein Tyrosine Phosphatase, Non-Receptor Type 11 Protein Tyrosine Phosphatase, Non-Receptor Type 6 Protein Tyrosine Phosphatases / physiology* Receptors, Antigen, T-Cell / physiology* Recombinant Fusion Proteins / physiology SH2 Domain-Containing Protein Tyrosine Phosphatases Structure-Activity Relationship Transfection src Homology Domains |
| IF | 17.794 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 2 |
| 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 | DT40(RCB1464) SHP2^(-) DT40(RCB1502) |