Skip to main content
. 2013 Dec 31;289(7):3842–3855. doi: 10.1074/jbc.M113.515254

FIGURE 7.

FIGURE 7.

α6 integrin is the upstream regulator of the IGF-1R signaling pathway that enables low levels of caspase-3 activation to signal lens epithelial cell differentiation initiation. Differentiation initiation of lens epithelial cells require low levels of caspase-3 activity that are induced downstream of the canonical mitochondrial death pathway, which acts as a molecular switch in inducing lens epithelial cell differentiation initiation. Previous studies have shown that an IGF-1R/NFκB (p65/p50 complex)-mediated survival signal regulates the level of caspase-3 activity for its role in lens differentiation. Here we show that α6 integrin transactivates IGF-1R to regulate the level of caspase-3 activity through the induction of survival proteins in the Bcl-2 (Bcl-2 and Bcl XL) and IAP families (ch-IAP-1, X-IAP, and survivin). This pathway allows caspase-3 to play a non-apoptotic role in lens epithelial cell differentiation initiation. Our findings show a novel role for the α6 integrin/IGF-1R coordinated survival signal in lens differentiation by modulating the activation of caspase-3.