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 cytoskeletal dynamics. However, little is known about the mechanisms by which Rho GTPases induce cytoskeletal changes. Complex systems of actin depolymerization/polymerization, actin-myosin interactions and coupling of actin binding proteins with actin filaments regulate cytoskeleton remodeling. p-2l activated kinase (PAK), an effector molecule activated by Rac and Cdc42, has been previously implicated in cytoskeletal changes. Here we describe two novel substrates of PAK, which are important regulators of the cytoskeleton. Myosin light chain kinase (MLCK), which mediates phosphorylation of the regulatory myosin light chain and thus controls contractility and tension of the cytoskeleton, is phosphorylated by PAK both in vitro and in vivo. This phosphorylation results in decreased activity of MLCK and, hence, decreased contractility. Lim-kinase phosphorylates and inactivates the small actin binding protein cofilin/actin depolymerizing factor (ADF). PAK phosphorytates Lim-kinase and increases Lim-kinase-mediated phosphorylation of cofilin 10 fold, thereby promoting actin polymerization.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 1999
- Accession Number
- ADA382496
Entities
People
- Luraynne C. Sanders
Organizations
- Scripps Research