Fernandez C.A.,Karp Family Research Bldg |
Roy R.,Karp Family Research Bldg |
Roy R.,Harvard University |
Lee S.,Massachusetts Institute of Technology |
And 7 more authors.
Journal of Biological Chemistry | Year: 2010
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. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc. Source