A positive feedback loop between Gli1 and tyrosine kinase Hck amplifies shh signaling activities in medulloblastoma.

ABSTRACT: Sonic hedgehog (Shh) signaling is critical during normal development, and the abnormal activation of the Shh pathway is involved in many human cancers. As a target gene of the Shh pathway and as a transcription activator downstream of Shh signaling, Gli1 autoregulates and increases Shh signaling output. Gli1 is one of the key oncogenic factors in Shh-induced tumors such as medulloblastoma. Gli1 is posttranslationally modified, but the nature of the active form of Gli1 was unclear. Here we identified a Src family kinase Hck as a novel activator of Gli1. In Shh-responsive NIH3T3 cells, Hck interacts with Gli1 and phosphorylates multiple tyrosine residues in Gli1. Gli1-mediated target gene activation was significantly enhanced by Hck with both kinase activity-dependent and -independent mechan

SUBMITTER: Shi X 

PROVIDER: S-EPMC4670963 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature