title: Regulation of myosin-IIA assembly and Mts1 binding by heavy chain phosphorylation.
abstract: Previous studies suggested that heavy chain phosphorylation regulates non-muscle myosin-II assembly in an isoform-specific manner, affecting the assembly of myosin-IIB, but not myosin-IIA. We re-examined the effects of heavy chain phosphorylation on myosin-IIA filament formation and also examined mts1 binding. We demonstrated that heavy chain phosphorylation by either protein kinase C (PKC) or casein kinase 2 (CK2) inhibits the assembly of myosin-IIA into filaments. PKC phosphorylation had no affect on mts1 binding, but CK2 phosphorylation decreased the affinity of mts1 for the myosin-IIA rod by approximately 6.5-fold. Mts1 destabilized PKC-phosphorylated myosin-IIA filaments and inhibited the assembly of myosin-IIA monomers with maximal inhibition of assembly and promotion of disassembly occurring at a molar ratio of one mts1 dimer per myosin-IIA rod. At this molar ratio, mts1 only weakly disassembled CK2-phosphorylated myosin-IIA filaments and weakly inhibited the assembly of CK2-phosphorylated myosin-IIA monomers. These observations demonstrate that CK2 phosphorylation of the myosin-IIA heavy chain protects against mts1-induced filament disassembly and inhibition of assembly, and suggest that heavy chain phosphorylation provides an additional level of regulation for the mts1-myosin-IIA interaction.
authors.affiliation: Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA.
authors.forename: Natalya G
authors.initials: NG
authors.lastname: Dulyaninova
authors.forename: Vladimir N
authors.initials: VN
authors.lastname: Malashkevich
authors.forename: Steven C
authors.initials: SC
authors.lastname: Almo
authors.forename: Anne R
authors.initials: AR
authors.lastname: Bresnick
mesh_terms: D008841:Actin Cytoskeleton / Q000201:enzymology / Q000378:metabolism; D047390:Casein Kinase II / Q000737:chemistry / Q000378:metabolism; D003198:Computer Simulation; D006801:Humans; D008958:Models, Molecular; D018995:Myosin Heavy Chains / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D024507:Nonmuscle Myosin Type IIA / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D010766:Phosphorylation; D011108:Polymers / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D011493:Protein Kinase C / Q000737:chemistry / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D017434:Protein Structure, Tertiary; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D010446:Peptide Fragments; D011108:Polymers; D020033:Protein Isoforms; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C077591:S100A4 protein, human; D047390:Casein Kinase II; D011493:Protein Kinase C; D024507:Nonmuscle Myosin Type IIA; D018995:Myosin Heavy Chains