J.Jpn. Surg. Soc.. 97(11): 964-969, 1996

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Feature topic

TRANSPLANTATION IMMUNOLOGY AND IMMUNOSUPPRESSIVE DRUG

Tyrosine kinases (TK) and G proteins act as second, essengers for intracellular signal trunsduction. TK activates the cascade of protein phosphorylation. G proteins are heterodimer complex with α, β, and γ subunits. PLC activated by GTP-binding α 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 aynthesizes 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 phosphorilation of I-κB to release NF-κB. 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-κB into nucleus. FTY720 induces lymphocyte-specific apoptosis, independently on Fas-antigen expressions, by modulating bc1-2 genes.

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