NOTCH1 NOTCH1:DLK1 NOTCH1 binds DLK1 Authored: Egan, SE, Orlic-Milacic, M, 2011-11-14 DLK1 is a Delta-like transmembrane protein with six extracellular EGF repeats and a short intracellular tail. DLK1 is encoded by a paternally imprinted gene and, based on mouse studies, is implicated in many developmental processes, such as adipogenesis, hematopoiesis, differentiation of adrenal gland and other neuroendocrine cells, as well as development of the central nervous system. Mice lacking Dlk1 exhibit growth retardation and obesity. Based on studies done in mice and flies, NOTCH1 and DLK1 interact to form a complex, most likely in cis, which results in the inhibition of NOTCH1 signaling by preventing NOTCH1 interaction with DLL and JAG ligands (Baladron et al. 2005, Bray et al. 2008). Besides its inhibitory role, DLK1 may function as a coactivator for NOTCH receptors. DLK1 possesses a Delta and OSM-11 motif (DOS), which has been found in C. elegans proteins that facilitate Notch activation in trans by DSL family ligands. The mammalian DLK1 can substitute for OSM-11 protein in C. elegans development (Komatsu et al. 2008). Edited: D'Eustachio, P, 2012-02-06 Edited: Orlic-Milacic, M, 2012-02-10 Pubmed15652348 Pubmed18237417 Pubmed18700817 Reactome Database ID Release 431980130 Reactome, http://www.reactome.org ReactomeREACT_118570 Reviewed: Haw, R, 2012-02-06