Inhibition of Lymphocyte Kinase Lck and Phosphatidylinositol 3-kinase by a Novel Immunosuppressant, Lymphostin.

DOI Web Site Web Site PubMed 57 References

Search this article

Description

  Lck is a Src-family tyrosine kinase that is expressed predominantly in T cells, where it plays important roles in T-cell activation. Lymphostin was isolated from Streptomyces sp. as an inhibitor of Lck. As previously reported, lymphostin inhibited Lck (IC50 0.05 μM) and the mixed lymphocyte reaction (IC50 0.009 μM). We have now examined the mechanism of inhibition by lymphostin. Lymphostin inhibited protein-tyrosine kinase activity in Jurkat T cells, demonstrating the effectiveness of the compound at the cellular level. Furthermore, lymphostin suppressed delayed-type hypersensitivity in mice. However, the inhibitory activity against Lck at the cellular level was weaker than that against the mixed lymphocyte reaction. Thus, we examined the effects of lymphostin on other kinases. Interestingly, lymphostin also inhibited phosphatidylinositol 3-kinase (IC50 0.001 μM). Consequently, we conclude that lymphostin inhibits the mixed lymphocyte reaction and delayed-type hypersensitivity not only through the blockade of Lck, but through the blockade of phosphatidylinositol 3-kinase as well.<br>

Journal

References(57)*help

See more

Keywords

Details 詳細情報について

Report a problem

Back to top