Metastasis-associated protein Mts1 (S100A4) inhibits CK2-mediated phosphorylation and self-assembly of the heavy chain of nonmuscle myosin

• Published in: Biochimica et biophysica acta Vol. 1498; no. 2; pp. 252 - 263
• Main Authors: Kriajevska, Marina, Bronstein, Igor B., Scott, David J., Tarabykina, Svetlana, Fischer-Larsen, Margrethe, Issinger, Olaf-Georg, Lukanidin, Eugene
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 20.12.2000
• Subjects: Blood Platelets - drug effects; Blood Platelets - metabolism; Casein Kinase II; Cells, Cultured; Enzyme Activation - drug effects; Humans; Myosin Heavy Chains - chemistry; Myosin Heavy Chains - metabolism; Nonmuscle myosin; Peptide Mapping; Phosphorylation - drug effects; Protein kinase CK2; Protein-Serine-Threonine Kinases - antagonists & inhibitors; Protein-Serine-Threonine Kinases - biosynthesis; Protein-Serine-Threonine Kinases - chemistry; S100 Calcium-Binding Protein A4; S100 Proteins - metabolism; S100 Proteins - pharmacology; S100A4; Self-assembly of myosin; Solubility; Trypsin; S100A4; Protein kinase CK2; Self-assembly of myosin; Nonmuscle myosin
• ISSN: 0167-4889; 0006-3002; 1879-2596
• DOI: 10.1016/S0167-4889(00)00100-2

A role for EF-hand calcium-binding protein Mts1 (S100A4) in the phosphorylation and the assembly of myosin filaments was studied. The nonmuscle myosin molecules form bipolar filaments, which interact with actin filaments to produce a contractile force. Phosphorylation of the myosin plays a regulatory role in the myosin assembly. In the presence of calcium, Mts1 binds at the C-terminal end of the myosin heavy chain close to the site of phosphorylation by protein kinase CK2 (Ser1944). In the present study, we have shown that interaction of Mts1 with the human platelet myosin or C-terminal fragment of the myosin heavy chain inhibits phosphorylation of the myosin heavy chain by protein kinase CK2 in vitro. Mts1 might also bind directly the β subunit of protein kinase CK2, thereby modifying the enzyme activity. Our results indicate that myosin oligomers were disassembled in the presence of Mts1. The short C-terminal fragment of the myosin heavy chain was totally soluble in the presence of an equimolar amount of Mts1 at low ionic conditions (50 mM NaCl). Depolymerization was found to be calcium-dependent and could be blocked by EGTA. Our data suggest that Mts1 can increase myosin solubility and therefore suppress its assembly.