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.
Dulyaninova
Natalya G
NG
Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
House
Reniqua P
RP
Betapudi
Venkaiah
V
Bresnick
Anne R
AR
D019943:Amino Acid Substitution; D047390:Casein Kinase II / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology; D022001:Focal Adhesions / Q000187:drug effects; D006801:Humans; D050505:Mutant Proteins / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000378:metabolism*; D024507:Nonmuscle Myosin Type IIA / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D010768:Phosphoserine / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D020033:Protein Isoforms / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D011554:Pseudopodia / Q000187:drug effects; D012995:Solubility / Q000187:drug effects
D050505:Mutant Proteins; D020033:Protein Isoforms; D010768:Phosphoserine; D004815:Epidermal Growth Factor; D047390:Casein Kinase II; D024507:Nonmuscle Myosin Type IIA; D018995:Myosin Heavy Chains