Hematopoietic adaptors in T-cell signaling: potential applications to transplantation.
Recent advances have been made in understanding the basis of T-cell signaling with the identification of hematopoeitic-specific adaptor proteins, or molecular scaffolds that facilitate protein complex formation and the integration of signals from the surface of T cells. Their potential relevance as targets in the modulation of transplantation relates to their immune-cell-specific expression and their ability to integrate signals needed for T-cell/APC conjugate formation, cytokine production and the clonal expansion of T cells. While LAT, GADS and SLP-76 are needed for TcR-induced cytokine production, the adaptors ADAP, VAV and SKAP-55 play specialized roles in the regulation of integrin adhesion and conjugation. Given the importance of these functions to the reactivity of T cells to allodeterminants of tissue grafts (GvH), and in the recognition and destruction of leukemic cells (GvL), these adaptors represent a new generation of potential targets in the modulation of transplantation.
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D006085:Graft Survival; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D007166:Immunosuppressive Agents; D008954:Models, Biological; D016377:Organ Transplantation / Q000379:methods*; D010750:Phosphoproteins / Q000502:physiology; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism*; D014181:Transplantation Immunology
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D016207:Cytokines; C409587:GRAP2 protein, human; D007166:Immunosuppressive Agents; D010750:Phosphoproteins; C108336:SKAP1 protein, human; C092947:SLP-76 signal Transducing adaptor proteins