title: Cell adhesion-dependent serine 85 phosphorylation of paxillin modulates focal adhesion formation and haptotactic migration via association with the C-terminal tail domain of talin.
abstract: Integrin-mediated adhesion to extracellular matrix proteins is dynamically regulated during morphological changes and cell migration. Upon cell adhesion, protein-protein interactions among molecules at focal adhesions (FAs) play major roles in the regulation of cell morphogenesis and migration. Although tyrosine phosphorylation of paxillin is critically involved in adhesion-mediated signaling, the significance of paxillin phosphorylation at Ser-85 and the mechanism by which it regulates cell migration remain unclear. In this study, we examined how Ser-85 phosphorylation of paxillin affects FA formation and cell migration. We found that paxillin phosphorylation at Ser-85 occurred during HeLa cell adhesion to collagen I and was concomitant with tyrosine phosphorylation of both focal adhesion kinase and talin. However, the non-phosphorylatable S85A mutant of paxillin impaired cell spreading, FA turnover, and migration toward collagen I but not toward serum. Furthermore, whereas the (presumably indirect) interaction between paxillin and the C-terminal tail of talin led to dynamic FAs at the cell boundary, S85A paxillin did not bind talin and caused stabilized FAs in the central region of cells. Together, these observations suggest that cell adhesion-dependent Ser-85 phosphorylation of paxillin is important for its interaction with talin and regulation of dynamic FAs and cell migration.
authors: Department of Pharmacy, Research Institute of Pharmaceutical Sciences, Medicinal Bioconvergence Research Center, College of Pharmacy, College of Medicine, Seoul National University, Seoul 151-742, Korea.
authors: Tae Kyoung
authors: TK
authors: Kwak
authors: Mi-Sook
authors: MS
authors: Lee
authors: Jihye
authors: J
authors: Ryu
authors: Yoon-Ju
authors: YJ
authors: Choi
authors: Minkyung
authors: M
authors: Kang
authors: Doyoung
authors: D
authors: Jeong
authors: Jung Weon
authors: JW
authors: Lee
mesh_terms: D019943:Amino Acid Substitution; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D022001:Focal Adhesions / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D020125:Mutation, Missense; D051419:Paxillin / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D017434:Protein Structure, Tertiary; D012694:Serine / Q000235:genetics / Q000378:metabolism
chemical_list: D024042:Collagen Type I; C496061:PXN protein, human; D051419:Paxillin; D012694:Serine