Smoothened-dependent and -independent pathways in mammalian noncanonical Hedgehog signaling.

ABSTRACT: Hedgehog proteins are pivotal morphogens acting through a canonical pathway involving first activation of ligand binding to Patched followed by alleviation of Smoothened receptor inhibition, leading to activation of Gli transcription factors. Noncanonical Hedgehog signaling remains poorly characterized but is thought to be mainly dependent on Smoothened. However, Smoothened inhibitors have yielded only partial success in combating Hedgehog signal transduction-dependent cancer, suggesting that noncanonical Smoothened-independent pathways also are clinically relevant. Moreover, several Smoothened-dependent effects (e.g. neurite projection) do not require transcriptional activation, further suggesting biological importance of noncanonical Smoothened-dependent pathways. We comprehensive

SUBMITTER: Faria AVS 

PROVIDER: S-EPMC6597826 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature