| First Author | Cuevas BD | Year | 2003 |
| Journal | EMBO J | Volume | 22 |
| Issue | 13 | Pages | 3346-55 |
| PubMed ID | 12839996 | Mgi Jnum | J:84276 |
| Mgi Id | MGI:2667264 | Doi | 10.1093/emboj/cdg322 |
| Citation | Cuevas BD, et al. (2003) MEKK1 regulates calpain-dependent proteolysis of focal adhesion proteins for rear-end detachment of migrating fibroblasts. EMBO J 22(13):3346-55 |
| abstractText | Herein, we define how MEKK1, a MAPK kinase kinase, regulates cell migration. MEKK1 is associated with actin fibers and focal adhesions, localizing MEKK1 to sites critical in the control of cell adhesion and migration. EGF-induced ERK1/2 activation and chemotaxis are inhibited in MEKK1-/- fibroblasts. MEKK1 deficiency causes loss of vinculin in focal adhesions of migrating cells, increased cell adhesion and impeded rear-end detachment. MEKK1 is required for activation of the cysteine protease calpain and cleavage of spectrin and talin, proteins linking focal adhesions to the cytoskeleton. Inhibition of ERK1/2 or calpain, but not of JNK, mimics MEKK1 deficiency. Therefore, MEKK1 regulates calpain-mediated substratum release of migrating fibroblasts. |
