also called magic roundabout, is a ~150 kDa glycoprotein belonging to
the ROBO family (1). ROBOs are molecular guidance receptors that
typically interact with Slit ligands to regulate axon guidance and
neuronal migration (2). Unlike other family members, ROBO4 is mainly
restricted to the vascular endothelium (1, 2). Expression in early
hematopoietic progenitors is also reported (3). The human ROBO4 cDNA
encodes 1012 amino acids (aa), including a 27 aa signal sequence, a
440 aa extracellular domain (ECD) containing two C2‑type Ig domains and
two fibronectin type III (FNIII) domains, a transmembrane domain and an
intracellular domain. ROBO4 diverges from other ROBOs in the number of
Ig, FNIII and cytoplasmic CC domains (1, 4). Within the ECD, human ROBO4
shares 80%, 80%, 87% and 88% aa identity with mouse, rat, bovine and
canine ROBO4, respectively. Vascular endothelial ROBO4 is expressed at
highest levels in during development and vascular remodeling, including
tumor angiogenesis (1, 2, 4 ‑ 6). It is proposed to contribute to
vascular stability. Consistent with this, endogenous ROBO4 is
concentrated in the vascular stalk and sprouts rather than tip cells and
appears to protect newly formed blood vessels against VEGF‑induced
vascular leak (6 ‑ 9). ROBO4 binding of Slit proteins has been variably
reported, and when detected may be mediated by ROBO4/ROBO1 heterodimers
(2, 4 ‑ 7, 9 ‑ 13). ROBO4 is also variably reported to stimulate or
inhibit cell migration or filopodia formation (2, 4 ‑ 13). Effects on
cell movement may be mediated through intracellular binding of WASP‑,
Ras/Rac/Rho‑, Mena‑, Src‑ or Paxillin‑related proteins, all of which
affect the cytoskeleton (5 ‑ 7, 10 ‑ 12). Recombinant soluble ROBO4 ECD
can antagonize endothelial cell migration and in vivo
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Legg, J.A. et al. (2008) Angiogenesis 11:13.
Shibata, F. et al. (2009) Stem Cells 27:183.
Park, K.W. et al. (2003) Dev. Biol. 261:251.
Seth, P. et al. (2005) Biochem. Biophys. Res. Commun. 332:533.
Jones, C.A. et al. (2008) Nat. Med. 14:448.
Jones, C.A. et al. (2009) Nat. Cell Biol. 11:1325.
Chen, H. et al. (2010) Adv. Exp. Med. Biol. 664:457.
London, N.R. et al. (2009) J. Thromb. Haemost. 7:57.
Verissimo, A.R. et al. (2009) Biochem. Soc. Trans. 37:1214.
Sheldon, H. et al. (2009) FASEB J. 23:513.
Kaur, S. et al. (2008) BMC Cell Biol. 9:61.
Suchting, S. et al. (2005) FASEB J. 19:121.
This product is for research use only and is not approved for use in humans or in clinical diagnosis. Primary Antibodies are guaranteed for 1 year from date of receipt.
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