Metastasis-associated Mts1 (S100A4) protein modulates protein kinase C phosphorylation of the heavy chain of nonmuscle myosin

TY - JOUR

T1 - Metastasis-associated Mts1 (S100A4) protein modulates protein kinase C phosphorylation of the heavy chain of nonmuscle myosin

AU - Kriajevska, Marina

AU - Tarabykina, Svetlana

AU - Bronstein, Igor

AU - Maitland, Norman

AU - Lomonosov, Mikhail

AU - Hansen, Klaus

AU - Georgiev, Georgii

AU - Lukanidin, Eugene

PY - 1998/4/17

Y1 - 1998/4/17

N2 - Mts1 protein (S100A4 according to a new classification) has been implicated in the formation of the metastatic phenotype via regulation of cell motility and invasiveness. Previously we have demonstrated that Mts1 protein interacted with the heavy chain of nonmuscle myosin in a calcium- dependent manner. To elucidate the role of the Mts1-myosin interaction, we mapped the Mts1-binding region on the myosin heavy chain molecule. We prepared proteolytically digested platelet myosin and a series of overlapped myosin heavy chain protein fragments and used them in a blot overlay with Mts1 protein. Here we report that the Mts1-binding site is located within a 29-amino acid region, at the C-terminal end of the myosin heavy chain (between 1909-1937 amino acids). Two-dimensional phosphopeptide analysis showed that Mts1 protein inhibits protein kinase C phosphorylation of the platelet myosin heavy chain at Ser-1917. We hypothesize that Mts1 protein regulates cytoskeletal dynamics of the metastatic cells through modulation of the myosin phosphorylation by protein kinase C in calcium-dependent fashion.

AB - Mts1 protein (S100A4 according to a new classification) has been implicated in the formation of the metastatic phenotype via regulation of cell motility and invasiveness. Previously we have demonstrated that Mts1 protein interacted with the heavy chain of nonmuscle myosin in a calcium- dependent manner. To elucidate the role of the Mts1-myosin interaction, we mapped the Mts1-binding region on the myosin heavy chain molecule. We prepared proteolytically digested platelet myosin and a series of overlapped myosin heavy chain protein fragments and used them in a blot overlay with Mts1 protein. Here we report that the Mts1-binding site is located within a 29-amino acid region, at the C-terminal end of the myosin heavy chain (between 1909-1937 amino acids). Two-dimensional phosphopeptide analysis showed that Mts1 protein inhibits protein kinase C phosphorylation of the platelet myosin heavy chain at Ser-1917. We hypothesize that Mts1 protein regulates cytoskeletal dynamics of the metastatic cells through modulation of the myosin phosphorylation by protein kinase C in calcium-dependent fashion.

UR - http://www.scopus.com/inward/record.url?scp=0032540233&partnerID=8YFLogxK

U2 - 10.1074/jbc.273.16.9852

DO - 10.1074/jbc.273.16.9852

M3 - Journal article

C2 - 9545325

AN - SCOPUS:0032540233

SN - 0021-9258

VL - 273

SP - 9852

EP - 9856

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

IS - 16

ER -