Meta-Biol

• Pathways

Although direct phosphorylation of GLI1 by PKA has not been demonstrated, deletion of the putative PKA sites abrogates the interaction of GLI1 with beta-TrCP and stabilizes GLI1 protein levels; similarly, treatment of GLI1-expressing cells with PKA inhibitors delays the kinetics of GLI1 degradation (Huntzicker et al, 2006). These data are consistent with a role for PKA-mediated phosphorylation in promoting the proteasome-dependent degradation of GLI1 in the absence of Hh signal, as is the case for GLI2 and GLI3 (Huntzicker et al, 2006; Tempe et al, 2006; Pan and Wang, 2007; Pan et al, 2009). Potential roles for CK2 and GSK3 in promoting the phosphorylation-dependent degradation of GLI1 have not been investigated.