Ligand-Induced Cis-Inhibition of Notch Signaling: The Role of an Extracellular Region of Serrate

Abstract

Cellular development can be controlled by communication between adjacent cells mediated by the highly conserved Notch signaling system. A cell expressing the Notch receptor on one cell can be activated in trans by ligands on an adjacent cell leading to alteration of transcription and cellular fate. Ligands also have the ability to inhibit Notch signaling, and this can be accomplished when both receptor and ligands are coexpressed in cis on the same cell. The manner in which cis-inhibition is accomplished is not entirely clear but it is known to involve several different protein domains of the ligands and the receptor. Some of the protein domains involved in trans-activation are also used for cis-inhibition, but some are used uniquely for each process. In this work, the involvement of various ligand regions and the receptor are discussed in relation to their contributions to Notch signaling.