This application describes studies to investigate the mechanism underlying the regulation of cell growth by the protein tyrosine phosphatase SHP-1. SHP-1 is a SH2-domain containing tyrosine phosphatase that has been shown in a number of systems to negatively regulate receptor-mediated cell signaling pathways and therefore negatively regulate cell growth. It has been most extensively studied in the context of hematopoietic/cytokine receptors, FCgRIIB and MCH class I receptors expressed on NK cells, where SHP-1 is recruited to the tyrosine phosphorylated receptor and activated. The investigator has identified nuclear proteins that are associated with SHP-1 and has demonstrated that SHP-1 is found in the nucleus. Dr. Yi proposes to investigate: 1) the role of two C-terminal tyrosine residues in the nuclear localization of SHP-1; 2) the cell cycle dependence on the interaction of SHP-1 with its nuclear binding partners; and 3) the role of these binding partners in activating the phosphatase activity of SHP-1. Through these studies the investigator proposes to identify a nuclear function for SHP-1 that contributes to its role as a negative regulator of cell growth.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM058893-04
Application #
6490248
Study Section
Experimental Immunology Study Section (EI)
Program Officer
Marino, Pamela
Project Start
1999-01-01
Project End
2003-12-31
Budget Start
2002-01-01
Budget End
2002-12-31
Support Year
4
Fiscal Year
2002
Total Cost
$158,529
Indirect Cost
Name
Cleveland Clinic Lerner
Department
Type
DUNS #
017730458
City
Cleveland
State
OH
Country
United States
Zip Code
44195