Ulk3 function in Shh signaling pathway

A model of Ulk3 function in Shh signaling pathway. In the absence of Shh, Sufu forms a complex with Ulk3 that possibly interacts with cytoskeleton through its MIT domain. The complex binds full-length Gli2 through Sufu, protecting it from proteosomal degradation. Ulk3 is not catalytically active but plays a regulatory role. The Ulk3-Sufu complex contributes to C-terminal processing of Gli2 probably through recruiting PKA, glycogen synthase kinase 3β (GSK3β), and casein kinase 1 (CK1) kinases to full-length Gli2. This results in generation of Gli2Rep that may enter the nucleus and inhibit its target gene expression. In the presence of Shh, Ulk3-Sufu-Gli2 complex dissociates, Ulk3 activates itself by autophosphorylation and phosphorylates full-length Gli2. This contributes to generation of Gli2Act, which translocates to the nucleus and activates its target genes. Other molecule(s) indicated as a question mark (?), for instance, Stk36, may participate in the regulation of Gli2 activity by converting it to transcriptional activator or repressor forms depending on the cellular context and strength of Shh signaling.

Publication

Dual Function of UNC-51-like Kinase 3 (Ulk3) in the Sonic Hedgehog Signaling Pathway. (2010) Alla Maloverjan, et al. J Biol Chem. 2010 Sep 24;285(39):30079-30090. Figure: F7. All organisms Homo sapiens Mus musculus Rattus norvegicus Danio rerio

Disease mentions