Convergent mechanisms in Wnt and Hedgehog signaling.

Authors

Benjamin R Myers, Jesse G Zalatan, David M Virshup

Published in

Science signaling. Volume 19. Issue 945. Pages eadz5029. Jul 07, 2026. Epub Jul 07, 2026.

Abstract

The Wnt and Hedgehog (Hh) pathways are cornerstones of tissue and organ biology and are implicated in numerous diseases. Wnt and Hh signaling share multiple mechanistic features, including lipidated ligands, specialized ligand delivery systems, atypical G protein-coupled receptors, and transcriptional effectors controlled by phosphorylation-dependent inhibition. Here, we highlight work showing that tethered pseudosubstrate inhibition of kinases is a core mechanism governing intracellular signal transmission in both pathways. These parallels suggest that Wnt and Hh have converged on a shared regulatory logic, enabling them to encode specific functional outputs while using molecules shared with numerous other cascades. This mode of signaling may extend to other pathways where cell-surface receptors directly regulate kinase activity.

PMID:
42412914
Bibliographic data and abstract were imported from PubMed on 08 Jul 2026.

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