The Eph family of receptor tyrosine kinases and their cognate ligands, the Ephrins, form a coordinated program of cell contact-mediated migration control, polarity establishment, and tissue architecture development. Specifically, the ligand Ephrin-A1 has been shown to regulate cell morphology and motility through the activation of EphA receptors, which signal to the PI3K pathway to induce cell retraction. MEFs with PI3K subunit p85β knockout (p85β−/−) exhibited markedly reduced cell retraction following Ephrin-A1 stimulation. Ephrin-A1 also serves as an inhibitory substrate for cell spreading and migration. Moreover, Ephrin-A1 treatment results in the dephosphorylation of paxillin and induces the reorganization of phospho-paxillin-containing focal adhesions. The Ephrin-A1 regulated paxillin dephosphorylation is phosphatase dependent, but p85β independent. The present study serves to demonstrate a novel molecular signaling pathways that regulate Ephrin-A1-regulated cell retraction and interaction to the substrate.
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This article is part of the celebration dedicated to Dr. Shu Chien 80th birthday, for his outstanding leadership and significant contributions in the field of physiology, cell biology, molecular biology, including cell biomechanics and mechanotransduction. We also greatly appreciate Dr. Shu Chien’s mentorship for the past years and his incredible dedication not only to the scientific research, education, as well as the services to scientific communities. This work was supported in part by National Institutes of Health Research Grants HL085159, HL104402, and HL106579 (to S.C.). This study is done under the supervisor of Dr. Shu Chien. Dr. Chien’s guidance is greatly appreciated. We appreciate Dr. Feng GS (Burnham Institute, La Jolla, CA) provided Shp2 deficient MEFs.
Associate Editor Edward Guo oversaw the review of this article.
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An Ephrin-A1/Fc-coated surface inhibits cell spreading. Wildtype, p85β−/−, or Shp2 deficient MEFs were seeded on tissue culture dish surfaces coated with 1 μg/cm2 of Ephrin-A1/Fc, and allowed to spread for 8 h. Images were captured of the same field of view at 3, 6, and 8 h post-seeding. SHP2 deficient MEF cells are generated in Dr. Feng GS group. In brief, these MEFs with SHP2 exon3-SH2 domain deletion fail to bind to their targets, which in turn lead to the functional deficiency. Ephrin-A1/Fc inhibited wildtype (the 1st row) and Shp2 deficient (the 3rd row) MEF spreading, whereas p85β−/− showed an improved cell spreading and migration on Ephrin-A1/Fc surface (the 2nd row) (TIFF 2931 kb)
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Fero, D., Wang, KC., Nguyen, P. et al. Ephrin-A1 Regulates Cell Remodeling and Migration. Cel. Mol. Bioeng. 4, 648–655 (2011). https://doi.org/10.1007/s12195-011-0212-9