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Fig. 9. A dominant-negative ILK rescues the EphA1-mediated spreading defect. (A) HEK293 cells were co-transfected with EphA1-FLAG and myc-tagged ILK, CAT or ANK (see Fig. 1), and anti-myc immunoprecipitates (IP) were subjected to anti-FLAG (upper) and anti-myc (lower) immunoblotting. Specific bands are indicated by arrows. (B) HEK293 (293) Mock and WT-EphA1–FLAG (EphA1) cells were transfected with GFP (control) or ANK-GFP, and their expression was confirmed by anti-GFP immunoblotting. (C) The same set of cells as is shown in B was subjected to spreading assays. (D) A model for the regulation of cell spreading by EphA1. Ephrin-A1 activates EphA1, which recruits ILK to the SAM domain of EphA1. ECM activates the FAK-PI3K-ILK cascade. EphA1 could activate FAK but also inhibit ILK downstream of FAK. ILK suppresses Rho-ROCK but its de-inhibition by EphA1 through ILK inhibition results in the spreading defect. The kinase activity of ILK is negatively regulated by EphA1 kinase (through a direct or indirect mechanism). The suppression of Rac1 and activation of the RhoA-ROCK pathway might result in the increase of cell contractility, and inhibition of cell spreading and migration.
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