VASP

PLC-gamma1 is activated by dual phosphorylation on the tyrosine residues at positions 771, 783 and 1254 by Itk and ZAP-70 (step 14). Phosphorylated PLC-gamma1 subsequently detaches from LAT and SLP-76 and translocates to the plasma membrane by binding to phosphatidylinositol-4,5-bisphosphate (PIP2) via its PH domain (step 15). PLC-gamma1 goes on to hydrolyse PIP2 to second messengers DAG and IP3. These second messengers are involved in PKC and NF-kB activation and calcium mobilization (step 16)

In addition to regulating axon guidance, ROBO1 and ROBO2 receptors are also implicated in regulation of proliferation and transition of primary to intermediate neuronal progenitors through a poorly characterized cross-talk with NOTCH-mediated activation of HES1 transcription (Borrell et al. 2012).

Thalamocortical axon extension is regulated by neuronal activity-dependent transcriptional regulation of ROBO1 transcription. Lower neuronal activity correlates with increased ROBO1 transcription, possibly mediated by the NFKB complex (Mire et al. 2012).

It is suggested that the homeodomain transcription factor NKX2.9 stimulates transcription of ROBO2, which is involved in regulation of motor axon exit from the vertebrate spinal code (Bravo-Ambrosio et al. 2012).

Of the four ROBO proteins, ROBO4 is not involved in neuronal system development but is, instead, involved in angiogenesis. The interaction of ROBO4 with SLIT3 is involved in proliferation, motility and chemotaxis of endothelial cells, and accelerates formation of blood vessels (Zhang et al. 2009)