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J Biol Chem. 2010 Dec 31;285(53):41886-95. doi: 10.1074/jbc.M110.166439. Epub 2010 Oct 12.

The anti-angiogenic peptide, loop 6, binds insulin-like growth factor-1 receptor.

Author information

1
Vascular Biology Program, Children's Hospital Boston, Boston, Massachusetts 02115, USA.

Abstract

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.

PMID:
20940305
PMCID:
PMC3009916
DOI:
10.1074/jbc.M110.166439
[Indexed for MEDLINE]
Free PMC Article

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