title: Interaction of phospholipase C-gamma1 with villin regulates epithelial cell migration.
abstract: Tyrosine-phosphorylated villin regulates actin dynamics, cell morphology, and cell migration. Previously, we identified four tyrosine phosphorylation sites in the amino-terminal domain of villin. In this study we report six new sites in the carboxyl-terminal region of the villin core. With this study we document all phosphorylatable tyrosine residues in villin and map them to functions of villin. In this study, we identify for the first time the functional relevance of the carboxyl-terminal domains of the villin core. Expression of the carboxyl-terminal phosphorylation site mutant, as well as the villin truncation mutant S1-S3, inhibited cell migration in HeLa and Madin-Darby canine kidney Tet-Off cells, confirming the role of the carboxyl-terminal phosphorylation sites in villin-induced cell migration. The carboxyl-terminal phosphorylation sites were found to be critical for the interaction of villin with its ligand phospholipase C-gamma1 and for its localization to the developing lamellipodia in a motile cell. The results presented here elucidate the molecular basis for tyrosine-phosphorylated villin-induced changes in cell motility.
authors.affiliation: Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA.
authors.forename: Alok
authors.initials: A
authors.lastname: Tomar
authors.forename: Sudeep
authors.initials: S
authors.lastname: George
authors.forename: Pallavi
authors.initials: P
authors.lastname: Kansal
authors.forename: Yaohong
authors.initials: Y
authors.lastname: Wang
authors.forename: Seema
authors.initials: S
authors.lastname: Khurana
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002465:Cell Movement; D053938:DNA Fragmentation; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology*; D006367:HeLa Cells; D006801:Humans; D008840:Microfilament Proteins / Q000737:chemistry / Q000502:physiology*; D008969:Molecular Sequence Data; D051966:Phospholipase C gamma / Q000378:metabolism / Q000502:physiology*; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid
chemical_list: D008840:Microfilament Proteins; C026615:villin; D051966:Phospholipase C gamma