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Slit-Robo

Slit-Robo is the name of a cell signaling pathway with many diverse functions including axon guidance and angiogenesis.

Slit refers to a secreted protein which is most widely known as a repulsive axon guidance cue, and Robo to its transmembrane protein receptor. There are four different Robos and three Slits in vertebrates: Robo1, Robo2, Robo3/Rig-1, and Robo4, and Slit1, Slit2, Slit3. There are three Robos and a single Slit in Drosophila. The corresponding Slit and Robo homologues in C. elegans are Slt and Sax-3, respectively.

Slits are characterized by four distinct domains, each containing variable numbers of leucine-rich repeats (LRRs), seven to nine EGF repeats, an ALPS domain (Agrin, Perlecan, Laminin, Slit), and a cysteine knot. Robos are characterized by five Ig-like domains, three fibronectin type III (FNIII) repeats, a transmembrane portion, and an intracellular tail with up to four conserved cytoplasmic motifs: CC0 (a potential site of tyrosine phosphorylation), CC1 (also a potential site of tyrosine phosphorylation and binds P3 domain of netrin-1 receptor DCC), CC2 (polyproline stretch; consensus binding site for Ena/Vasp proteins), and CC3 (polyproline stretch).