Proteolytic processing of SLIT

Stable Identifier
R-HSA-376149
Type
Reaction [transition]
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
General
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

The full length SLIT proteins are secreted and, when not bound to ROBO receptors, are indirectly associated with the plasma membrane via the extracellular matrix proteins. These full length SLITs undergo posttranslational modification and proteolytic processing to generate an N-terminal fragment (SLIT2-N) and a corresponding C-terminal fragment (SLIT2-C). SLIT2 is cleaved within the EGF repeats, between EGF5 and EGF6, by unknown proteases. Cleavage of SLIT proteins is evolutionarily conserved, although the molecular biological significance is unknown. The N-terminal fragment of SLIT2 stimulates growth and branching of dorsal root ganglia (DRG) axons, and this activity is opposed by un-cleaved SLIT. The stimulation of axon branching is mediated by ROBO receptors. Additional functional differences between the full-length and N-terminal forms have been discovered in their abilities to repel different populations of axons and dendrites. Finally, SLIT can attract migrating muscles in the fly, and also human endothelial cells, both via ROBO receptors (Brose et al. 1999, Wang et al. 1999).

SLIT C-terminal fragments may transduce signaling independently of ROBO receptors and Neuropilins (semaphorin receptors) by directly binding to Plexin A1 (Delloye-Bourgeois et al. 2015).

Literature References
PubMed ID Title Journal Year
10102268 Slit proteins bind Robo receptors and have an evolutionarily conserved role in repulsive axon guidance

Brose, K, Bland, KS, Wang, KH, Arnott, D, Henzel, W, Goodman, CS, Tessier-Lavigne, M, Kidd, T

Cell 1999
10102266 Biochemical purification of a mammalian slit protein as a positive regulator of sensory axon elongation and branching

Wang, KH, Brose, K, Arnott, D, Kidd, T, Goodman, CS, Henzel, W, Tessier-Lavigne, M

Cell 1999
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
peptidase activity of Unidentified protease [cytosol]
Physical Entity
Activity
Authored
Reviewed
Created
Cite Us!