c-Ras is required for the activation of the matrix metalloproteinases by concanavalin A in 3Y1 cells.

Concanavalin A (Con A) is known to trigger augmented secretion and proteolytic activation of the matrix metalloproteinases (MMPs) in fibroblasts. To study the signaling pathway critical for the activation of MMPs in fibroblasts, we examined the effects of dominant negative ras (S17N ras) expression under the control of conditionally inducible promoter in Con A-activated 3Y1 cells. We found that augmented secretion and proteolytic activation of MMP-2 and MMP-9 together with expression of MT1-MMP in Con A-activated 3Y1 were dramatically suppressed by S17N ras expression. These results strongly suggest that c-Ras plays a critical role in the augmented expression and proteolytic activation of MMPs in fibroblasts.