Myosin-IIA heavy-chain phosphorylation regulates the motility of MDA-MB-231 carcinoma cells.
In mammalian nonmuscle cells, the mechanisms controlling the localized formation of myosin-II filaments are not well defined. To investigate the mechanisms mediating filament assembly and disassembly during generalized motility and chemotaxis, we examined the EGF-dependent phosphorylation of the myosin-IIA heavy chain in human breast cancer cells. EGF stimulation of MDA-MB-231 cells resulted in transient increases in both the assembly and phosphorylation of the myosin-IIA heavy chains. In EGF-stimulated cells, the myosin-IIA heavy chain is phosphorylated on the casein kinase 2 site (S1943). Cells expressing green fluorescent protein-myosin-IIA heavy-chain S1943E and S1943D mutants displayed increased migration into a wound and enhanced EGF-stimulated lamellipod extension compared with cells expressing wild-type myosin-IIA. In contrast, cells expressing the S1943A mutant exhibited reduced migration and lamellipod extension. These observations support a direct role for myosin-IIA heavy-chain phosphorylation in mediating motility and chemotaxis.
Pubmed ID: 17567956 RIS Download
Amino Acid Substitution | Casein Kinase II | Cell Line, Tumor | Cell Movement | Epidermal Growth Factor | Focal Adhesions | Humans | Mutant Proteins | Myosin Heavy Chains | Nonmuscle Myosin Type IIA | Phosphorylation | Phosphoserine | Protein Binding | Protein Isoforms | Protein Transport | Pseudopodia | Solubility