Effect of Mts1 on the structure and activity of nonmuscle myosin II.
The mts1 gene codes for a 9 kDa protein belonging to the S100 subfamily of Ca2+-binding proteins and is known to play a role in metastasis. Its role in metastasis may be through cellular locomotion, as transfection of mts1 into mouse mammary adenocarcinoma cells increases cellular motility in modified Boyden chemotaxis chambers. The Mts1 protein interacts with nonmuscle myosin II in the presence of Ca2+ with an affinity of approximately 7.9 x 10(4) M-1 and an approximate stoichiometry of 3 mol of Mts1/mol of myosin heavy chain. No interaction was found with myosin I or myosin V. The binding site of Mts1 on myosin is in the rod region, particularly to the light meromyosin portion of the rod. To understand the mechanism by which Mts1 alters cellular motility, we examined its effect on myosin structure and activity. Cosedimentation analysis and electron microscopy suggest that Mts1 destabilizes myosin filaments. In the presence of Ca2+, Mts1 inhibits the actin-activated MgATPase activity of myosin in vitro. The data demonstrate an effect of Mts1 on both myosin structure and function, and suggest a route through which Mts1 affects motility as well as metastasis.
Ford
H L
HL
Department of Biochemistry and Cancer Center, University of Rochester, 601 Elmwood Avenue, Rochester, New York 14642, USA.
Silver
D L
DL
Kachar
B
B
Sellers
J R
JR
Zain
S B
SB
D001665:Binding Sites; D001792:Blood Platelets / Q000737:chemistry; D017301:Ca(2+) Mg(2+)-ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism* / Q000494:pharmacology; D002465:Cell Movement / Q000502:physiology; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D008854:Microscopy, Electron; D015879:Myosin Subfragments / Q000235:genetics / Q000378:metabolism; D009218:Myosins / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D009362:Neoplasm Metastasis; D010766:Phosphorylation; D011233:Precipitin Tests; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; D014461:Ultracentrifugation
D002135:Calcium-Binding Proteins; D015879:Myosin Subfragments; D011994:Recombinant Proteins; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C077591:S100A4 protein, human; D017301:Ca(2+) Mg(2+)-ATPase; D009218:Myosins; D002118:Calcium