The Essential Role of Protein Phosphatase-1 in Mitogenic Signaling and Breast Cancer
Abstract
Organization of the actin cytoskeleton is crucial for a diverse set of cell functions including cell division, intracellular signaling, cell shape, and motility. Cancerous cells demonstrate changes in cell adhesion and growth consistent with altered regulation of the actin cytoskeleton. Our research has focused on the regulation of protein phosphorylation, specifically signals mediated by protein phosphatase 1 (PPl), a serine/threonine phosphatase, in these processes. Current work is focused on a class of regulatory subunits, neurabin I and neurabin II, that direct PPl to the actin cytoskeleton. Neurabin I and neurabin II were cloned from rat tissue either as PPl or F-actin binding proteins and contain multiple domains. We have cloned homologs of these proteins from Xenopus laevis and C. elegans. The high degree of structural homology from worms to mammals in specific domains, such as the PPi binding domain and PDZ domain, begin to highlight regions most likely to be important for the in vivo function of these proteins in these diverse species. GFP-tagged constructs of full length neurabin I transfected into HEK-293 cells show that the full-length protein localizes to the actin cytoskeleton. A C-terminal truncation of the coiled-coil and PDZ domains also localizes neurabin I to the actin cytoskeleton and ca
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2000
- Accession Number
- ADA387640
Entities
People
- Carey Oliver
- Shirish Shenolikar
Organizations
- Duke University Hospital