[Transplantation immunology and immunosuppressive drug].
Tyrosine kinases (TK) and G proteins act as second, messengers for intracellular signal transduction. TK activates the cascade of protein phosphorylation. G proteins are heterodimer complex with alpha, beta, and gamma subunits. PLC activated by GTP-binding alpha subunit lyses membrane phosphatidyl inositol (PI), releasing diacyl glycerol (DAG) and inositol trisphosphate (IP3). IP3 releases calcium into cytoplasm to activate calcineurin, causing a NF-AT cytoplasmic factor (NF-ATc) to translocate to nucleus. DAG activates protein kinase C (PKC), which synthesizes another nuclear factor NF-ATn. When NF-ATc and NF-ATn assemble to form the complex on the promoter site of DNA, transcription of IL-2 mRNA begins. PKC also induces phosphorylation of I-kappa B to release NF-kappa B. The complex of CsA or FK506 with CyP or FKBP, respectively, inhibits the activation of calcineurin. FKBP-binding rapamycin inhibits cell proliferation and differentiation by inactivation of p70 s6 kinase. RS61443 and mizoribine influence specifically on the de novo pathway of purine biosynthesis. DSG may bind to Hsc 70 and inhibit the translocation of NF-kappa B into nucleus. FTY720 induces lymphocyte-specific apoptosis, independently on Fas-antigen expressions. by modulating bcl-2 genes.
Suzuki
S
S
National Children's Medical Research Center, Department of Experimental Surgery and Bioengineering, Tokyo, Japan.
D017209:Apoptosis / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D009696:Nucleic Acids / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology*; D014181:Transplantation Immunology
D007166:Immunosuppressive Agents; D009696:Nucleic Acids