Reactome | MMPs cleave HB-EGF

MMPs cleave HB-EGF

Stable Identifier

R-HSA-9624272

Type

Reaction [transition]

Species

Homo sapiens

Compartment

plasma membrane, extracellular region

ReviewStatus

5/5

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Estrogen-stimulation of ESR1 activates downstream signaling pathways that results in the release of HB-EGF in an IGF- MMP- and EGFR-dependent manner (Razandi et al, 2003; Song et al, 2004; Song et al, 2007; Santen et al, 2009). Based on studies in other systems, candidate MMPs for the cleavage of HB-EGF include MMP2, MMP3, MMP7 and MMP9 (Suzuki et al, 1997; Yu et al, 2002; Razandi et al, 2003). Although direct cleavage of HB-EGF by MMPs downstream of estrogen signaling has not been demonstrated, estrogen-stimulated signaling through EGFR is abrogated after treatment of cells with an HB-EGF neutralizing antibody (Razandi et al, 2003; Song et al, 2007).

Literature References

PubMed ID	Title	Journal	Year
19138696	Estrogen signals via an extra-nuclear pathway involving IGF-1R and EGFR in tamoxifen-sensitive and -resistant breast cancer cells Santen, RJ, Fan, P, Zhang, Z, Bao, Y, Song, RX, Yue, W	Steroids	2009
11825873	CD44 anchors the assembly of matrilysin/MMP-7 with heparin-binding epidermal growth factor precursor and ErbB4 and regulates female reproductive organ remodeling Yu, WH, Woessner, J, McNeish, JD, Stamenkovic, I	Genes Dev	2002
17525128	Estrogen signaling via a linear pathway involving insulin-like growth factor I receptor, matrix metalloproteinases, and epidermal growth factor receptor to activate mitogen-activated protein kinase in MCF-7 breast cancer cells Song, RX, Zhang, Z, Chen, Y, Bao, Y, Santen, RJ	Endocrinology	2007
12421825	Proximal events in signaling by plasma membrane estrogen receptors Razandi, M, Pedram, A, Park, ST, Levin, ER	J. Biol. Chem.	2003
9395517	Matrix metalloproteinase-3 releases active heparin-binding EGF-like growth factor by cleavage at a specific juxtamembrane site Suzuki, M, Raab, G, Moses, MA, Fernandez, CA, Klagsbrun, M	J Biol Chem	1997
14764897	The role of Shc and insulin-like growth factor 1 receptor in mediating the translocation of estrogen receptor alpha to the plasma membrane Song, RX, Barnes, CJ, Zhang, Z, Bao, Y, Kumar, R, Santen, RJ	Proc. Natl. Acad. Sci. U.S.A.	2004