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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29CA069530-05
Application #
6342003
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Program Officer
Cole, John S
Project Start
1997-04-01
Project End
2002-12-31
Budget Start
2001-01-01
Budget End
2001-12-31
Support Year
5
Fiscal Year
2001
Total Cost
$106,479
Indirect Cost
Name
University of Tennessee Knoxville
Department
Veterinary Sciences
Type
Schools of Veterinary Medicine
DUNS #
City
Knoxville
State
TN
Country
United States
Zip Code
37996
Song, Ping; Wei, Jinxiong; Wang, Hwa-Chain Robert (2005) Distinct roles of the ERK pathway in modulating apoptosis of Ras-transformed and non-transformed cells induced by anticancer agent FR901228. FEBS Lett 579:90-4
Song, Ping; Wei, Jinxiong; Plummer 3rd, Howard et al. (2004) Potentiated caspase-3 in Ras-transformed 10T1/2 cells. Biochem Biophys Res Commun 322:557-64
Mei, Jianxun; Hu, Hongbo; McEntee, Michael et al. (2003) Transformation of non-cancerous human breast epithelial cell line MCF10A by the tobacco-specific carcinogen NNK. Breast Cancer Res Treat 79:95-105
Fecteau, Kellie A; Mei, Jianxun; Wang, Hwa-Chain R (2002) Differential modulation of signaling pathways and apoptosis of ras-transformed 10T1/2 cells by the depsipeptide FR901228. J Pharmacol Exp Ther 300:890-9
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