The Canonical Notch Signaling Pathway: Unfolding the Activation Mechanism

Raphael Kopan, Ma Xenia G. Ilagan

Research output: Contribution to journalReview articlepeer-review

2754 Scopus citations


Notch signaling regulates many aspects of metazoan development and tissue renewal. Accordingly, the misregulation or loss of Notch signaling underlies a wide range of human disorders, from developmental syndromes to adult-onset diseases and cancer. Notch signaling is remarkably robust in most tissues even though each Notch molecule is irreversibly activated by proteolysis and signals only once without amplification by secondary messenger cascades. In this Review, we highlight recent studies in Notch signaling that reveal new molecular details about the regulation of ligand-mediated receptor activation, receptor proteolysis, and target selection.

Original languageEnglish
Pages (from-to)216-233
Number of pages18
Issue number2
StatePublished - Apr 17 2009


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