and specific aims): The goal of this project is to define the role that a specific receptor type tyrosine phosphatase (PTPase) plays in regulating epithelial cell proliferation and differentiation in developing and mature lung. Tyrosine PTPases dephosphorylate phospho-tyrosines on proteins that have been activated or inactivated (phosphorylated) by specific tyrosine kinases of which many are growth factor receptors. Thus, PTPases have the potential to regulate a variety of cell signaling events associated with development and cell differentiation. The application postulates that the transmembrane tyrosine phosphatase LAR may negatively regulate cell growth by interacting with growth factor receptors possessing intrinsic tyrosine kinase activities, and that this function is important in lung epithelial cells, especially during lung development.
The specific aims are to: 1) develop methods and reagents to alter biological activities of LAR and define their effects on epithelial cell proliferation and differentiation in a fetal lung organ culture system; 2) determine the potential roles of LAR in regulating cell proliferation and in modulating growth factor-mediated signal transduction; and 3) determine specific mechanism of LAR function by identifying and characterizing proteins with which LAR interacts.
| Wang, X; Weng, L P; Yu, Q (2000) Specific inhibition of FGF-induced MAPK activation by the receptor-like protein tyrosine phosphatase LAR. Oncogene 19:2346-53 |
| Matsui, R; Brody, J S; Yu, Q (1999) FGF-2 induces surfactant protein gene expression in foetal rat lung epithelial cells through a MAPK-independent pathway. Cell Signal 11:221-8 |
| Weng, L P; Wang, X; Yu, Q (1999) Transmembrane tyrosine phosphatase LAR induces apoptosis by dephosphorylating and destabilizing p130Cas. Genes Cells 4:185-96 |
| Weng, L P; Yuan, J; Yu, Q (1998) Overexpression of the transmembrane tyrosine phosphatase LAR activates the caspase pathway and induces apoptosis. Curr Biol 8:247-56 |
