Annexin II: a plasminogen-plasminogen activator co-receptor.
Fibrinolysis is a precisely orchestrated process in which fibrin-containing thrombi are solubilized. Several receptors regulate this process by localizing proteolytic activity to the cell surface. One such receptor is annexin II, a calcium and phospholipid-binding protein. Annexin II serves as a profibrinolytic coreceptor for both plasminogen and tissue plasminogen activator on the surface of endothelial cells and facilitates the generation of plasmin. The dysregulation of fibrinolytic assembly on endothelial cells may lead to atherothrombotic disease. In addition to its role in fibrinolysis at the surface of endothelial cells, annexin II may play other potential cellular roles. For example, the overexpression of annexin II on the surface of leukemic cells and cell lines derived from acute promyelocytic leukemia correlates with both the clinical manifestation of bleeding and the in vitro ability of the leukemic cells to generate plasmin. The abundant presence of annexin II on the surface of other cell types including monocytic cell lines and different cancer cells may contribute to their invasive potential through extracellular matrix either by generation of plasmin or, by plasmin-mediated proteolytic activation of other metalloproteinases. This dissolution of extracellular matrix may also cause the release of potent matrix-bound angiogenic factors such as VEGF and FGF. On the other hand, by increasing the pool of plasmin, a precursor to an important anti-angiogenic factor, angiostatin, and by fragmentation of collagen XVIII (a precursor to the anti-angigenic factor, endostatin) by plasmin-activated metalloproteases, annexin II could play a pivotal physiological role in the pro- and anti-angiogenic switch mechanism.
Kim
Jiyun
J
Department of Pediatrics, Weill Medical College of Cornell University, Box 45, 1300 York Avenue, New York, NY 10021, USA.
Hajjar
Katherine A
KA
D017306:Annexin A2 / Q000737:chemistry / Q000378:metabolism*; D017302:Annexins / Q000737:chemistry; D001161:Arteriosclerosis / Q000209:etiology; D005109:Extracellular Matrix / Q000378:metabolism; D006474:Hemorrhagic Disorders / Q000209:etiology; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000097:blood; D008264:Macrophages / Q000502:physiology; D010958:Plasminogen / Q000378:metabolism*; D010960:Plasminogen Activators / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator; D010959:Tissue Plasminogen Activator / Q000378:metabolism
D017306:Annexin A2; D017302:Annexins; C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D010958:Plasminogen; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator