| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1996: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1995: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Research Abstract |
To understand the signal transduction pathway from PKCdelta to a transcription factor, AP1, we first tried to identify acceptors for the signal from PKCdelta. West-western screening of an expression library constructed with mRNA of NIH3T3 cells arrow us to identify a novel PKCdelta-binding protein named SRBC.SRBC not only binds to but also phosphorylated by PKCdelta, and the SRBC mRNA increases in NIH3T3 cells when they are serum starved for 48 h. Furthermore, the over-expression of SRBC inhibits cell growth. These observations are consistent with our former observation that constitutive activation of PKCdelta inhibits cell growth. However, a question if SRBC is involved in the inhibition of cell growth by PKCdelta remains to be answered. On the other hand we also found that PKCdelta activates ERK,a member of MAP kinase, through c-Raf. It has been reported that ERK induces c-fos gene encoding a subunit of AP1, by activating a transcription factor E1k-1. Therefore, the activation of c-Raf and ERK by PKCd must be an important part of signal transduction from PKCdelta to AP1. The molecular mechanism for the activation of c-Raf by PKCdelta is a subject in feature. On the other hand, as an approach from the AP1 side, we investigate the signal transduction pathway to activate JNK-SAPK, which phosphorylates and activates c-Jun, an subunit of AP1. We found that a group of function unknown protein kinases, MLK (mixed lineage kinase)-related protein kinases, activate JNK-SAPK through SEKI-MKK4. Then, two questions arose : how the activity of MLK-related kinases is controlled and if PKC is involved in the control mechanism.
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