Role of palladin phosphorylation by extracellular signal-regulated kinase in cell migration.
Phosphorylation of actin-binding proteins plays a pivotal role in the remodeling of the actin cytoskeleton to regulate cell migration. Palladin is an actin-binding protein that is phosphorylated by growth factor stimulation; however, the identity of the involved protein kinases remains elusive. In this study, we report that palladin is a novel substrate of extracellular signal-regulated kinase (ERK). Suppression of ERK activation by a chemical inhibitor reduced palladin phosphorylation, and expression of active MEK alone was sufficient for phosphorylation. In addition, an in vitro kinase assay demonstrated direct palladin phosphorylation by ERK. We found that Ser77 and Ser197 are essential residues for phosphorylation. Although the phosphorylation of these residues was not required for actin cytoskeletal organization, we found that expression of non-phosphorylated palladin enhanced cell migration. Finally, we show that phosphorylation inhibits the palladin association with Abl tyrosine kinase. Taken together, our results indicate that palladin phosphorylation by ERK has an anti-migratory function, possibly by modulating interactions with molecules that regulate cell migration.
Division of Cancer Biology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
Eri
E
Asano
Masao
M
Maeda
Hitoki
H
Hasegawa
Satoko
S
Ito
Toshinori
T
Hyodo
Hong
H
Yuan
Masahide
M
Takahashi
Michinari
M
Hamaguchi
Takeshi
T
Senga
D001483:Base Sequence; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000378:metabolism*; D017931:DNA Primers; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D012694:Serine / Q000378:metabolism
D003598:Cytoskeletal Proteins; D017931:DNA Primers; C412722:PALLD protein, human; D010750:Phosphoproteins; D012694:Serine; D048049:Extracellular Signal-Regulated MAP Kinases