Ajuba's pre-LIM domain is the segment that associates with Grb-2's Src-homology 3 domain [9]. When this domain was overexpressed in serum-starved keratinocytes, a comparable elevation in pMAPK was observed (Figure 4F). As expected, the small peptide inhibitor that interrupts the Grb-2/Sos association blocked the effects. These data suggested that by elevating cytosolic Ajuba levels, Ajuba's pre-LIM domain may associate with Grb-2/Sos in a manner that stimulates its nucleotide exchange activity and leads to activation of the Ras-MAPK pathway. Although this pathway provides one mechanism by which Snail expression and proliferation may be coupled in skin epithelium, proliferative circuitries involving AJs are known to be complex and often interwoven. Future studies will be needed to systematically dissect these putative intricacies at a molecular level.