Metastasis-associated protein Mts1 (S100A4) inhibits CK2-mediated phosphorylation and self-assembly of the heavy chain of nonmuscle myosin.
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 beta 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.
Kriajevska
M
M
Department of Molecular Cancer Biology, Institute of Cancer Biology, Danish Cancer Society, Copenhagen, Denmark.
Bronstein
I B
IB
Scott
D J
DJ
Tarabykina
S
S
Fischer-Larsen
M
M
Issinger
O
O
Lukanidin
E
E
D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D047390:Casein Kinase II; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D018995:Myosin Heavy Chains / Q000737:chemistry / Q000378:metabolism*; D010449:Peptide Mapping; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000737:chemistry; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000378:metabolism* / Q000494:pharmacology; D012995:Solubility; D014357:Trypsin
D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C077591:S100A4 protein, human; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases; D014357:Trypsin; D018995:Myosin Heavy Chains