A horsefly saliva antigen 5-like protein containing RTS motif is an angiogenesis inhibitor.
The Ag5 proteins are the most abundant and immunogenic proteins in the venom secretory ducts of stinging insects. An antigen 5-like protein (named tabRTS) composed of 221 amino acid residues was purified and characterized from the salivary glands of the horsefly, Tabanus yao (Diptera, Tabanidae). Its cDNA was cloned from the cDNA library of the horsefly's salivary gland. TabRTS containing the SCP domain (Sc7 family of extracellular protein domain) was found in insect antigen 5 proteins. More interestingly, there is an Arg-Thr-Ser (RTS) disintegrin motif at the C-terminus of tabRTS. The RTS motif is positioned in a loop bracketed by cysteine residues as those found in RTS-disintegrins of Crotalidae and Viperidae snake venoms, which act as angiogenesis inhibitors. Endothelial Cell Tube formation assay in vitro and chicken chorioallantoic membrane (CAM) angiogenesis assay in vivo were performed as to investigate the effect of tabRTS on angiogenesis. It was found that tabRTS could significantly inhibit angiogenesis in vitro and in vivo. Anti-alpha(1)beta(1) monoclonal antibody could dose-dependently inhibit the anti-angiogenic activity of tabRTS. This result indicated that tabRTS possibly targets the alpha(1)beta(1) integrin to exert the anti-angiogenic activity as snake venom RTS-/KTS-disintegrins do. The current work revealed the first angiogenesis inhibitor protein containing RTS motif from invertebrates, a possible novel type of RTS-disintegrin.
Ma
Dongying
D
Biotoxin Units of Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, 32# Jiaochangdonglu, Kunming 650223, Yunnan, China.
Gao
Li
L
An
Shu
S
Song
Yuzhu
Y
Wu
Jing
J
Xu
Xueqing
X
Lai
Ren
R
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D020533:Angiogenesis Inhibitors / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply; D003001:Cloning, Molecular; D004175:Diptera / Q000737:chemistry*; D019483:Disintegrins; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects; D006801:Humans; D019476:Insect Proteins / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D039222:Integrin alpha1beta1 / Q000037:antagonists & inhibitors; D008969:Molecular Sequence Data; D018919:Neovascularization, Physiologic / Q000187:drug effects; D012463:Saliva / Q000737:chemistry*; D016415:Sequence Alignment
D020533:Angiogenesis Inhibitors; D019483:Disintegrins; D019476:Insect Proteins; D039222:Integrin alpha1beta1