Long terms goals of my research are to understand intracellular signaling controls altered upon cellular transformation and to restore the control to reverse the progress of cancers by suppressing the transforming features or driving transformed cells to apoptosis. Ultimate goal of this project is to identify signaling pathway (s) which link (s) cellular transformation to apoptosis. I have detected a novel serine/threonine protein kinase, p63 SAMK (src activated MBP kinase) whose activation may be involved in the process of apoptosis in normal and transformed cultures of avian and mammalian cells. Recently, we isolated a cDNA for a human protein kinase Krs-1 (kinase responsive to stress) who catalytic domain shares extensive homology with Ste20p family. Although Krs-1 shares many properties with p63 SAMK, discrepancy in the antigenicity and the analyzed peptide sequences raises a question of the homology between Krs-1 and p63 SAMK. In this project, I propose the following studies: 1. TO clarify the identify of chick p63 SAMK and the relationship with Krs-1 by isolation of the chick Krs-1 homologue cDNS and further study of the antigenic similarity between p63 SAMK and Krs-1. 2. To determine that nature of the activator of Krs-1/p63 SAMK in signaling cascade by biochemical study and chromatography. 3. To study the biological role of Krs-1/p63 SAMK in cellular transformation and apoptosis by expression of the gene products including the wild-type and mutant proteins and antisense messages in src-transformed or normal cells. Success of this project will advance our understanding of a particular signaling pathway linking cellular transformation to apoptosis-related cellular events.
