SMAD-Mediated Signaling During Prostate Growth and Development

The regulation of prostate morphogenesis has been shown to be regulated by signaling molecules from the transforming growth factor beta family. The binding of the TGF-beta ligand to the cell surface receptors lead to the activation of a kinase activity in the TGF-beta receptors. The propagation of the signal through the cytoplasm is mediated by the Smad family of molecules. The project has examined the phosphorylation of Smad 2 and Smad 3 in the absence of TGF-beta 3 signaling. The Smad 2 molecule is specifically not phosphorylated in the null mutant while Smad 3 is unaffected. The effect appears to specific for the beta 3 growth factor and rescue has not been shown with other TGF-beta family members. The null mutant represents a loss of function and in the absence of the growth factor no phosphorylation occurs, the effect appears to be growth factor specific. Current studies are examining the regulation of TGF-beta receptor kinase'activation and the potential of genetic rescue with Smad 2 overexpression. These studies should provide information specific for signaling mechanisms essential to glandular morphogenesis and relevant to mechanisms associated with uncontrolled glandular neoplasms.