Cell Adhesion, Signaling and Myosin in Breast Cancer
Abstract
Cytoskeleton remodeling is crucial in many cellular events, including cell adhesion, spreading and motility. The Rho family of small GTPases (Rho, Rac and Cdc42) are signal transducers that regulate cytoskeleton dynamics. However, little is known about the mechanisms by which Rho GTPases induce cytoskeletal changes. Here we show that Rac1 is important for cell spreading, a biological process in which the cytoskeleton is highly active. Overexpression of dominant negative or constitutively active Rac 1 significantly impairs the ability of the cells to spread. Rac activity is high only during early stages of spreading. The activity of p-21activating kinase (PAK), an effector molecule for Rac and Cdc42, is also high only during the early stages of spreading. Overexpression of catalytically active PAK inhibits cell spreading and decreases myosin phosphorylation. Myosin is the cytoskeleton protein which provides the force generating ability to the actin cytoskeleton. Treatment of cells with myosin inhibitors also inhibits cell spreading. In vitro and in vivo studies revealed a novel target for PAK, myosin light chain kinase (MLCK), the enzyme that phosphorylates the light chain of myosin II. Activated PAK phosphorylates MLCK and inhibits its ability to phosphorylate MLC. Thus, PAK appears to modulate cytoskeleton changes by phosphorylation and downregulation of MLCK.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2000
- Accession Number
- ADA388947
Entities
People
- Luraynne Sanders
Organizations
- Scripps Research