View source for Angiostatin

'''Angiostatin''' is a naturally occurring [[protein]] found in several animal species, including humans. It is an endogenous [[angiogenesis inhibitor]] (i.e., it blocks the growth of new [[blood vessel]]s), and it is currently undergoing [[clinical trial]]s for its use in anticancer therapy.<ref>http://www.clinicaltrials.gov/ct/gui/show/NCT00049790;jsessionid=91EE48B7C2F7D935B96F12E31D5609E3?order=1.</ref> 

==Structure==
Angiostatin is a 38 kDa fragment of a larger protein, [[plasmin]] (itself a fragment of [[plasminogen]]) enclosing three to five contiguous [[Kringle]] modules. Each module contains two small [[beta sheet]]s and three [[disulfide bond]]s. <ref>[http://www.jbc.org/cgi/content/abstract/271/46/29461 Kringle Domains of Human Angiostatin]; ''Journal of Biological Chemistry'', Volume 271, Number 46, Issue of November 15, 1996 pp. 29461-29467 </ref> <ref>[http://www.cell.com/content/article/abstract?uid=PII0092867494902003&session= Angiostatin: A novel angiogenesis inhibitor that mediates the suppression of metastases by a lewis lung carcinoma]; ''Cell'', Vol 79, 315-328, 21 October 1994 </ref>

==Generation==
Angiostatin is produced, for example, by autoproteolytic cleavage of plasminogen, involving extracellular disulfide bond [[Redox|reduction]] by [[phosphoglycerate kinase]]. Furthermore angiostatin can be cleaved from plasminogen by different [[metalloproteinases]] (MMPs), [[elastase]], prostata-specific [[antigen]] (PSA), 13 KD [[serine protease]], or 24KD [[endopeptidase]].

==Biological activity==
Angiostatin is known to bind a lot of proteins, especially to [[angiomotin]] and endothelial cell surface [[ATP synthase]] but also [[integrin]]s, [[annexin]] II, C-met receptor, NG2-proteoglycans, tissue-type plasminogen activator, chondroitin sulfate proteoglycans, and CD26. Also smaller fragments of angiostatin has been shown to bind several other proteins.  There is still considerable uncertainty on its mechanism of action, but it seems to involve for example inhibition of endothelial cell migration,<ref>Alexander Redlitz, Guenter Daum, E.Helene Sage; [http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowFulltext&ProduktNr=224160&Ausgabe=226163&ArtikelNr=25623 Angiostatin Diminishes Activation of the Mitogen-Activated Protein Kinases ERK-1 and ERK-2 in Human Dermal Microvascular Endothelial Cells]; ''Journal of Vascular Research'' 1999;36:28-34 (DOI: 10.1159/000025623)</ref>  [[proliferation]] and induction of [[apoptosis]]. It has been proposed that angiostatin activity is related, among other things, to the coupling of its mechanical and redox properties <ref>Fabio Grandi, Massimo Sandal, Giovanni Guarguaglini, Emidio Capriotti, Rita Casadio, Bruno Samorì [http://www3.interscience.wiley.com/cgi-bin/abstract/113343288/ABSTRACT?CRETRY=1&SRETRY=0 Hierarchical Mechanochemical Switches in Angiostatin]; ''ChemBioChem'' 2006;7(11):1774-1782</ref>

==References==
{{reflist|2}}

==External links==
* {{MeshName|Angiostatins}}

{{Angiogenic proteins}}
{{Beta globulins}}

[[Category:Angiogenesis inhibitors]]

{{protein-stub}}
{{WikiDoc Help Menu}}