This proposal centers on understanding the function of the 14-3-3 signaling molecule. The major goal is to establish that 14-3-3 specifically binds to serine-phosphorylated proteins and helps to assemble signaling complexes that regulate cell proliferation, differentiation, and cell motility. This hypothesis will be tested through three specific experimental aims. The first will be to assess the ability of 14-3-3 to bind to specific phosphoserine motifs in vivo (through the use of mutant forms of the Raf-1 kinase).
The second aim focuses on examining the role of 14-3-3 in Raf-1-mediated signal transduction through an analysis of the effects of specific 14-3-3 inhibitors on Xenopus laevis embryo development.
The third aim will then center on examining the role of 14-3-3 in the regulation of acting polymerization and cell motility in cultured fibroblasts. The expectation is that the results of these experiments will establish the importance of the 14-3-3 signaling molecules in cell growth regulation and development.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM054670-02
Application #
2701777
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Project Start
1997-05-01
Project End
2002-04-30
Budget Start
1998-05-01
Budget End
1999-04-30
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Barnes-Jewish Hospital
Department
Type
DUNS #
City
Saint Louis
State
MO
Country
United States
Zip Code
63110
Lau, Jeffrey M C; Wu, Chunlai; Muslin, Anthony J (2006) Differential role of 14-3-3 family members in Xenopus development. Dev Dyn 235:1761-76
Jirakulaporn, Tanawat; Muslin, Anthony J (2004) Cation diffusion facilitator proteins modulate Raf-1 activity. J Biol Chem 279:27807-15
Wu, Chunlai; Muslin, Anthony J (2002) Role of 14-3-3 proteins in early Xenopus development. Mech Dev 119:45-54
Bruinsma, Janelle J; Jirakulaporn, Tanawat; Muslin, Anthony J et al. (2002) Zinc ions and cation diffusion facilitator proteins regulate Ras-mediated signaling. Dev Cell 2:567-78
MacNicol, M C; Muslin, A J; MacNicol, A M (2000) Disruption of the 14-3-3 binding site within the B-Raf kinase domain uncouples catalytic activity from PC12 cell differentiation. J Biol Chem 275:3803-9
Xing, H; Zhang, S; Weinheimer, C et al. (2000) 14-3-3 proteins block apoptosis and differentially regulate MAPK cascades. EMBO J 19:349-58
Zhang, S; Xing, H; Muslin, A J (1999) Nuclear localization of protein kinase U-alpha is regulated by 14-3-3. J Biol Chem 274:24865-72