Cell migration is a key aspect of many normal and abnormal biological processes, including embryonic development, defense against infections, wound healing, and tumor cell metastasis. In this study we demonstrate that an epithelial cell actin-binding protein, villin, plays a crucial role in the process of cell migration. Overexpression of villin in doxycyline-regulated HeLa Tet-off and MDCK Tet-off cells enhanced cell migration. We further demonstrate that tyrosine phosphorylation of villin by c-src is required for villin-induced cell migration. Previously, we identified four tyrosine phosphorylation sites in the amino-terminal domain of villin. I further identified six new sites in the carboxylterminal region of the villin core. Collectively we have now documented all phosphorylatable tyrosine residues in villin and mapped them to villin’s functions. To further investigate the role of tyrosine phosphorylation sites in cell migration, we used phosphorylation site mutants (tyrosine to phenylalanine or tyrosine to glutamic acid) stably transfected in HeLa and MDCK Tet-off cells. We determined that tyrosine phosphorylation at amino-terminus of villin played an essential role in cell migration as well as in the reorganization of the actin cytoskeleton. The carboxyl-terminal phosphorylation sites were found to be critical for villin’s interaction with its ligand PLC-and for its localization to the developing lamellipodia in a motile cell. Collectively, these studies define how biophysical events such as cell migration are actuated by biochemical signaling pathways involving tyrosine phosphorylation of actin binding proteins, in this case villin.
","abstract_html":"<p>Cell migration is a key aspect of many normal and abnormal biological processes, including embryonic development, defense against infections, wound healing, and tumor cell metastasis. In this study we demonstrate that an epithelial cell actin-binding protein, villin, plays a crucial role in the process of cell migration. Overexpression of villin in doxycyline-regulated HeLa Tet-off and MDCK Tet-off cells enhanced cell migration. We further demonstrate that tyrosine phosphorylation of villin by c-src is required for villin-induced cell migration. Previously, we identified four tyrosine phosphorylation sites in the amino-terminal domain of villin. I further identified six new sites in the carboxylterminal region of the villin core. Collectively we have now documented all phosphorylatable tyrosine residues in villin and mapped them to villin’s functions. To further investigate the role of tyrosine phosphorylation sites in cell migration, we used phosphorylation site mutants (tyrosine to phenylalanine or tyrosine to glutamic acid) stably transfected in HeLa and MDCK Tet-off cells. We determined that tyrosine phosphorylation at amino-terminus of villin played an essential role in cell migration as well as in the reorganization of the actin cytoskeleton. The carboxyl-terminal phosphorylation sites were found to be critical for villin’s interaction with its ligand PLC-and for its localization to the developing lamellipodia in a motile cell. Collectively, these studies define how biophysical events such as cell migration are actuated by biochemical signaling pathways involving tyrosine phosphorylation of actin binding proteins, in this case villin.</p>","abstract_has_math":false,"creators":["Tomar, Alok"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Dissertation","degree_discipline":"Interdisciplinary Program","degree_department":null,"school":null,"contributors":["Seema Khurana, Ph.D."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2006,"date_issued":"2006-12-01T08:00:00Z","date_published":"2006-12-01T08:00:00Z","updated_at":"2026-07-24T05:00:17Z","subjects":["actin","villin","cell migration","tyrosine phosphorylation","wound healing","phosphomimetics","lamellipodia","EGF","PLC","PIP2","Amino Acids, Peptides, and Proteins","Chemicals and Drugs","Medical Cell Biology","Medical Sciences","Medicine and Health Sciences"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://dc.uthsc.edu/dissertations/271","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Seema Khurana, Ph.D."]},{"key":"dc:creator","label":"Author","values":["Tomar, Alok"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2016-06-17T07:00:00Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Interdisciplinary Program"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["actin","villin","cell migration","tyrosine phosphorylation","wound healing","phosphomimetics","lamellipodia","EGF","PLC","PIP2","Amino Acids, Peptides, and Proteins","Chemicals and Drugs","Medical Cell Biology","Medical Sciences","Medicine and Health Sciences"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://dc.uthsc.edu/dissertations/271"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Cell migration is a key aspect of many normal and abnormal biological processes, including embryonic development, defense against infections, wound healing, and tumor cell metastasis. In this study we demonstrate that an epithelial cell actin-binding protein, villin, plays a crucial role in the process of cell migration. Overexpression of villin in doxycyline-regulated HeLa Tet-off and MDCK Tet-off cells enhanced cell migration. We further demonstrate that tyrosine phosphorylation of villin by c-src is required for villin-induced cell migration. Previously, we identified four tyrosine phosphorylation sites in the amino-terminal domain of villin. I further identified six new sites in the carboxylterminal region of the villin core. Collectively we have now documented all phosphorylatable tyrosine residues in villin and mapped them to villin’s functions. To further investigate the role of tyrosine phosphorylation sites in cell migration, we used phosphorylation site mutants (tyrosine to phenylalanine or tyrosine to glutamic acid) stably transfected in HeLa and MDCK Tet-off cells. We determined that tyrosine phosphorylation at amino-terminus of villin played an essential role in cell migration as well as in the reorganization of the actin cytoskeleton. The carboxyl-terminal phosphorylation sites were found to be critical for villin’s interaction with its ligand PLC-and for its localization to the developing lamellipodia in a motile cell. Collectively, these studies define how biophysical events such as cell migration are actuated by biochemical signaling pathways involving tyrosine phosphorylation of actin binding proteins, in this case villin.
"]},{"key":"dc:title","label":"Title","values":["Tyrosine Phosphorylation of Villin: Effects on Actin Dynamics, Cell Morphology and Cell Migration"]}]}],"canonical_facts":{"dc:contributor":["Seema Khurana, Ph.D."],"dc:creator":["Tomar, Alok"],"dc:date.available":["2016-06-17T07:00:00Z"],"dc:description.abstract":["Cell migration is a key aspect of many normal and abnormal biological processes, including embryonic development, defense against infections, wound healing, and tumor cell metastasis. In this study we demonstrate that an epithelial cell actin-binding protein, villin, plays a crucial role in the process of cell migration. Overexpression of villin in doxycyline-regulated HeLa Tet-off and MDCK Tet-off cells enhanced cell migration. We further demonstrate that tyrosine phosphorylation of villin by c-src is required for villin-induced cell migration. Previously, we identified four tyrosine phosphorylation sites in the amino-terminal domain of villin. I further identified six new sites in the carboxylterminal region of the villin core. Collectively we have now documented all phosphorylatable tyrosine residues in villin and mapped them to villin’s functions. To further investigate the role of tyrosine phosphorylation sites in cell migration, we used phosphorylation site mutants (tyrosine to phenylalanine or tyrosine to glutamic acid) stably transfected in HeLa and MDCK Tet-off cells. We determined that tyrosine phosphorylation at amino-terminus of villin played an essential role in cell migration as well as in the reorganization of the actin cytoskeleton. The carboxyl-terminal phosphorylation sites were found to be critical for villin’s interaction with its ligand PLC-and for its localization to the developing lamellipodia in a motile cell. Collectively, these studies define how biophysical events such as cell migration are actuated by biochemical signaling pathways involving tyrosine phosphorylation of actin binding proteins, in this case villin.
"],"dc:identifier":["https://dc.uthsc.edu/dissertations/271"],"dc:subject":["actin","villin","cell migration","tyrosine phosphorylation","wound healing","phosphomimetics","lamellipodia","EGF","PLC","PIP2","Amino Acids, Peptides, and Proteins","Chemicals and Drugs","Medical Cell Biology","Medical Sciences","Medicine and Health Sciences"],"dc:title":["Tyrosine Phosphorylation of Villin: Effects on Actin Dynamics, Cell Morphology and Cell Migration"],"thesis:degree_discipline":["Interdisciplinary Program"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T05:00:17Z"}