Spitz (protein)

Spitz is produced as a transmembrane protein in the endoplasmic reticulum. There it associates with a cargo receptor called Star and is trafficked to the Golgi. In the Golgi, Spitz is cleaved by a protease called Rhomboid, which releases Spitz to be trafficked to the cell membrane and released out of the cell.^[1] From here it can bind EGFR on the surface of other cells, activating the receptor. Alternatively, Spitz can be bound and inactivated by Argos, inhibiting EGFR activation.^[2]

Spitz is responsible for activating signaling of the Drosophila epidermal growth factor receptor (DER) and is involved in the development of the embryos, eyes, and wings of fruit flies. Spitz can be sequestered and prevented from binding to DER by the protein Argos (Aos) which then inhibits the epidermal growth factor receptor pathway.^[3] Over-expression of epidermal growth factor receptors contribute to human cancers, so the sequestering of activating ligands may be useful in developing ways to diminish EGFR ligands for cancer treatment.^[2]

The protein Spitz is structurally similar to transforming growth factor-α (TGF-α) and is a homologue of TGF-α, along with other proteins found in Drosophila such as Gurken and Keren.^[1] These proteins are processed by Star, a transmembrane protein, and Rhomboid (Rho), a protease. Spitz binds to and regulates the epidermal growth factor receptor.^[4]