| Budget Amount *help |
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1998: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1997: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Research Abstract |
MST(MKN-28-derived nonreceptor serine/threonine kinase) is a member of MLK (mixed lineage kinase) whose function was unknown. We have shown that most of members of MLK family including MST activate JNK/SAPK when over-expressed in COS1 cells. Furthermore, by using recombinant MST protein, we have shown that MST directly phosphorylates and activates SEK1, an activator of JNK/SAPK.This finding indicates the members of MLK family act as MAPKKK in JNK/SAPK pathway. By using the in vitro reconstitution system of MST-JNK pathway, we found an MST-dependent JNK activator other than SEK1 in COS1 cell lysate. This second substrate of MST was identified as MKK7, a new member of MAPKK-class proteinkinase reported by other groups. Notably, MST activates MKK7 more efficiently than SEK1, while MEKK1, another MAPKKK activates both at similar extent. Since an expression of limited amount of MST can strongly induce JNK activation in several culture cell lines, the expression level of MST must be regulated tightly. Rather high expression of MST and MKK7 was observed in the nerve tissues of normal mouse embryo, indicating the contribution of MST-JNK signaling pathway in nerve cell differentiation. MST is also expressed in several cancer cell lines and we have found that MST can induce a VEGF promoter. We are now testing a function of MST in tumor angiogensis.
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