Smad-Mediated Signaling During Prostate Growth and Development
Abstract
The regulation of prostate morphogenesis is regulated by signaling molecules from the transforming growth factor beta family. The binding of the TGF-beta ligand to the cell surface receptors leads to the activation of a kinase activity in the TGF-beta receptors. The Smad family of molecules mediates the propagation of the signal through the cytoplasm. In the absence of TGF beta no signal is initiated. The null mutation of TGF-beta3 can be specifically rescued at the molecular level by over expression of Smad 2. The rescue is correlated both with the quantity of Smad 2 produced through the over expression and the quantity of Smad 2 that is phosphorylated. The mechanism for Smad 2 phosphorylation could be through activation of the receptor kinases by another growth factor or, through an alternative phosphorylation pathway. The ability to rescue the growth factor deficient phenotype through induction of a downstream effector molecule provides new insight into this regulatory pathway. The potential exists to develop strategies to activate the signal transduction mechanism in the absence of the growth factor and circumvent the deficiency. These results on the basic understanding of the signaling pathway will lead to new strategies for therapeutic intervention to alter cell growth and differentiation that may lead to neoplastic events.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2003
- Accession Number
- ADA419304
Entities
People
- Charles F. Shuler
Organizations
- University of Southern California