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

• Published in: The Journal of biological chemistry Vol. 287; no. 33; pp. 27499 - 27509
• Main Authors: Kwak, Tae Kyoung, Lee, Mi-Sook, Ryu, Jihye, Choi, Yoon-Ju, Kang, Minkyung, Jeong, Doyoung, Lee, Jung Weon
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 10.08.2012; American Society for Biochemistry and Molecular Biology
• Subjects: Adhesion; Amino Acid Substitution; Cell Adhesion - physiology; Cell Movement - physiology; Collagen Type I - genetics; Collagen Type I - metabolism; Focal Adhesion; Focal Adhesions - genetics; Focal Adhesions - metabolism; HeLa Cells; Humans; Invasion; Migration; Morphology; Mutation, Missense; Paxillin; Paxillin - genetics; Paxillin - metabolism; Phosphorylation - physiology; Protein Phosphorylation; Protein Structure, Tertiary; Serine - genetics; Serine - metabolism; Signal Transduction; Talin; Focal Adhesion; Signal Transduction; Migration; Morphology; Talin; Protein Phosphorylation; Adhesion; Paxillin; Invasion
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M111.323360

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. Background: Paxillin, a focal adhesion (FA) adaptor, functions in migration, although how Ser-85 phosphorylation affects migration is unknown. Results: Phosphorylation of paxillin at Ser-85 is critical for its association with talin, which regulates FA formation along the cell boundary and haptotactic migration. Conclusion: Paxillin Ser-85 phosphorylation regulates FA formation and migration. Significance: Paxillin Ser-85 phosphorylation coordinates FA dynamics for migration.