Rhomboid cleaves Star to regulate the levels of secreted Spitz.

Intracellular trafficking of the precursor of Spitz (Spi), the major Drosophila EGF receptor (EGFR) ligand, is facilitated by the chaperone Star, a type II transmembrane protein. This study identifies a novel mechanism for modulating the activity of Star, thereby influencing the levels of active Spi ligand produced. We demonstrate that Star can efficiently traffic Spi even when present at sub-stoichiometric levels, and that in Drosophila S(2)R(+) cells, Spi is trafficked from the endoplasmic reticulum to the late endosome compartment, also enriched for Rhomboid, an intramembrane protease.

Unidirectional Notch signaling depends on continuous cleavage of Delta.

Unidirectional signaling from cells expressing Delta (Dl) to cells expressing Notch is a key feature of many developmental processes. We demonstrate that the Drosophila ADAM metalloprotease Kuzbanian-like (Kul) plays a key role in promoting this asymmetry. Kul cleaves Dl efficiently both in cell culture and in flies, and has previously been shown not to be necessary for Notch processing during signaling.

TMF/ARA160 is a BC-box-containing protein that mediates the degradation of Stat3.

TMF/ARA160 is a Golgi resident protein whose cellular functions have not been conclusively revealed. Herein we show that TMF/ARA160 can direct the proteasomal degradation of the key cell growth regulator - Stat3. TMF/ARA160 was dispersed in the cytoplasm of myogenic C2C12 cells that were grown under low-serum conditions.

Intracellular trafficking by Star regulates cleavage of the Drosophila EGF receptor ligand Spitz.

Spitz (Spi) is a TGFalpha homolog that is a cardinal ligand for the Drosophila EGF receptor throughout development. Cleavage of the ubiquitously expressed transmembrane form of Spi (mSpi) precedes EGF receptor activation. We show that the Star and Rhomboid (Rho) proteins are necessary for Spi cleavage in Drosophila cells.