TY - JOUR
T1 - The anti-angiogenic peptide, Loop 6, binds insulin-like growth factor-1 receptor
AU - Fernandez, Cecilia A.
AU - Roy, Roopali
AU - Lee, Sunyoung
AU - Yang, Jiang
AU - Panigrahy, Dipak
AU - Van Vliet, Krystyn J.
AU - Moses, Marsha A.
PY - 2010/12/31
Y1 - 2010/12/31
N2 - Tissue inhibitors of metalloproteinases (TIMPs), the endogenous inhibitors of matrix metalloproteinases, have been shown to possess biological functions that are independent of their ability to inhibit matrix metalloproteinases. We have previously shown that the C-terminal domain of TIMP-2 and, in particular, Loop 6 inhibit capillary endothelial cell proliferation and angiogenesis both in vitro and in vivo. To elucidate the mechanism by which Loop 6 inhibits angiogenesis, we sought to determine whether its biological effects were the result of a known TIMP-2 protein-protein interaction or of a receptor-mediated event. In this study, we identify insulin-like growth factor-1 receptor as a binding partner of Loop 6/TIMP-2 and characterize this interaction on the endothelial cell surface and the consequences of this interaction on downstream receptor signaling.
AB - Tissue inhibitors of metalloproteinases (TIMPs), the endogenous inhibitors of matrix metalloproteinases, have been shown to possess biological functions that are independent of their ability to inhibit matrix metalloproteinases. We have previously shown that the C-terminal domain of TIMP-2 and, in particular, Loop 6 inhibit capillary endothelial cell proliferation and angiogenesis both in vitro and in vivo. To elucidate the mechanism by which Loop 6 inhibits angiogenesis, we sought to determine whether its biological effects were the result of a known TIMP-2 protein-protein interaction or of a receptor-mediated event. In this study, we identify insulin-like growth factor-1 receptor as a binding partner of Loop 6/TIMP-2 and characterize this interaction on the endothelial cell surface and the consequences of this interaction on downstream receptor signaling.
UR - http://www.scopus.com/inward/record.url?scp=78650662557&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78650662557&partnerID=8YFLogxK
U2 - 10.1074/jbc.M110.166439
DO - 10.1074/jbc.M110.166439
M3 - Article
C2 - 20940305
AN - SCOPUS:78650662557
SN - 0021-9258
VL - 285
SP - 41886
EP - 41895
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 53
ER -