Notch and the DSL Notch ligands Delta and Serrate/Jagged are glycoproteins with a single transmembrane domain. The extracellular domain (ECD) of both Notch receptors and Notch ligands contains numerous epidermal growth factor (EGF)-like repeats which are post-translationally modified by a variety of glycans. Inactivation of a subset of genes that encode glycosyltransferases which initiate and e...

Two glycosyltransferases that transfer sugars to EGF domains, OFUT1 and Fringe, regulate Notch signaling. However, sites of O-fucosylation on Notch that influence Notch activation have not been previously identified. Moreover, the influences of OFUT1 and Fringe on Notch activation can be positive or negative, depending on their levels of expression and on whether Delta or Serrate is signaling t...

Mammalian Notch receptors contain 29-36 epidermal growth factor (EGF)-like repeats that may be modified by protein O-fucosyltransferase 1 (Pofut1), an essential component of the canonical Notch signaling pathway. The Drosophila orthologue Ofut1 is proposed to function as both a chaperone required for stable cell surface expression of Notch and a protein O-fucosyltransferase. Here we investigate...

The trans-admittance-mode (TAM) might act as a transforming bridge for voltage-mode to current-mode conversion. In this study a new low voltage operated electronically tunable TAM biquad filter structure realizing all the seven standard filtering functions namely; low-pass (LP), band-pass (BP), high-pass (HP), regular-notch (RN), low-pass-notch (LPN), high-pass-notch (HPN) and all-pass (AP) fro...

In this paper, accumulation of plastic deformation of AISI 1045 steel plates with circular cutouts under cyclic axial loading is studied. Loading was applied under force-control conditions. Experimental tests were performed using a Zwick/Roell servo hydraulic machine. Under force-control loading with nonzero mean force, plastic strain was accumulated in continuous cycles called ratcheting. Nume...

Compartments are units of cell lineage that subdivide territories with different developmental potential. In Drosophila, the wing and haltere discs are subdivided into anterior and posterior (A/P) compartments, which require the activity of Hedgehog, and into dorsal and ventral (D/V) compartments, needing Notch signaling. There is enrichment in actomyosin proteins at the compartment boundaries,...

Notch in Invertebrate Development. Notch proteins are highly conserved transmembrane receptors that are involved in cell fate regulation in invertebrates (1). While Notch receptors are initially synthesized as single polypep-tide chains proteolytic processing results in the formation of a heterodimeric receptor in which the extracellular domain is noncovalently attached to the transmembrane and...

Multicellular development requires the correct spatial and temporal regulation of cell division and differentiation. These processes are frequently coordinated by the activities of various signaling pathways such as Notch signaling. From a screen for modifiers of Notch signaling in Drosophila we have identified the RNA helicase Belle, a recently described component of the RNA interference pathw...

BACKGROUND Ligand-induced proteolytic cleavage and internalization of the plasma membrane receptor Notch leads to its activation. Ligand-independent, steady-state internalization of Notch, however, does not lead to activation. The mechanism by which downstream effectors discriminate between these bipartite modes of Notch internalization is not understood. Nedd4 is a HECT domain-containing E3 ub...

AIMS Notch signalling is essential for blood vessel formation. During angiogenesis, the Notch ligand DLL4 on the leading tip cell activates Notch receptors on the adjacent stalk cells. DLL4-Notch signalling is impaired by the Notch ligand JAG1 in endothelial cells. The Delta/Serrate/Lag2 (DSL) domain of the Notch ligands binds to the EGF-like repeats 11-13 of the Notch receptor. This study aime...