The in vitro activity of ADAM‐10 is inhibited by TIMP‐1 and TIMP‐3

Amour, Augustin; Knight, Christopher G.; Webster, Ailsa; Slocombe, Patrick M.; Stephens, Paul E.; Knäuper, Vera; Docherty, Andrew; Murphy, Gillian

doi:10.1016/s0014-5793(00)01528-3

Cited by 365 publications

(273 citation statements)

References 26 publications

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“…However, the majority of proteins that undergo regulated shedding appear to be cleaved by TACE [Arribas and Borroto, 2002]. TIMP-3 inhibits both ADAM10 and TACE, whereas TIMP-1 inhibits ADAM10 but not TACE [Amour et al, 1998;Amour et al, 2000]. Both these ADAMs are expressed in HEK cells [Slack et al, 2001], and our results could suggest that collagen-dependent DDR1 shedding is mediated either by TACE alone, which would account for the resistance of the response to TIMP-1, or by both TACE and ADAM10.…”

Section: Discussionmentioning

confidence: 69%

Collagen type I selectively activates ectodomain shedding of the discoidin domain receptor 1: Involvement of Src tyrosine kinase

Slack

Siniaia

Blusztajn

2006

J of Cellular Biochemistry

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The discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase that is highly expressed in breast carcinoma cells. Upon binding to collagen, DDR1 undergoes autophosphorylation followed by limited proteolysis to generate a tyrosine phosphorylated C-terminal fragment (CTF). Although it was postulated that this fragment is formed as a result of shedding of the N-terminal ectodomain, collagen-dependent release of the DDR1 extracellular domain has not been demonstrated. We now report that, in conjunction with CTF formation, collagen type I stimulates concentration-dependent, saturable shedding of the DDR1 ectodomain from two carcinoma cell lines, and from transfected cells. In contrast, collagen did not promote cleavage of other transmembrane proteins including the amyloid precursor protein (APP), ErbB2, and E-cadherin. Collagen-dependent tyrosine phosphorylation and proteolysis of DDR1 in carcinoma cells were reduced by a pharmacologic Src inhibitor. Moreover, expression of a dominant negative Src mutant protein in human embryonic kidney cells inhibited collagen-dependent phosphorylation and shedding of co-transfected DDR1. The hydroxamate-based metalloproteinase inhibitor TAPI-1 (tumor necrosis factor-α protease inhibitor-1), and tissue inhibitor of metalloproteinase (TIMP)-3, also blocked collagen-evoked DDR1 shedding, but did not reduce levels of the phosphorylated CTF. Neither shedding nor CTF formation were affected by the γ-secretase inhibitor, L-685,458. The results demonstrate that collagen-evoked ectodomain cleavage of DDR1 is mediated in part by Src-dependent activation or recruitment of a matrix-or disintegrin metalloproteinase, and that CTF formation can occur independently of ectodomain shedding. Delayed shedding of the DDR1 ectodomain may represent a mechanism that limits DDR1-dependent cell adhesion and migration on collagen matrices. Keywords zinc-dependent metalloproteinase; amyloid precursor protein; tyrosine phosphorylation; TIMP (tissue inhibitor of metalloproteinase)

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Section: Discussionmentioning

confidence: 69%

Collagen type I selectively activates ectodomain shedding of the discoidin domain receptor 1: Involvement of Src tyrosine kinase

Slack

Siniaia

Blusztajn

2006

J of Cellular Biochemistry

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“…ADAM10 has been shown to be inhibited by tissue inhibitor of metalloproteases (TIMPs) 24 through the activity of their NTR module 24,25 . Because Sfrp1/2 contain an NTR module 8 , we postulated that Sfrp1/2 may normally down-regulate the activity of ADAM10.…”

Section: Adam10 Inhibition Rescues the Sfrp Ko Retinal Phenotypementioning

confidence: 99%

SFRPs act as negative modulators of ADAM10 to regulate retinal neurogenesis

et al. 2011

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It is well established that embryonic mouse retinal neurogenesis requiresNotch and Wnt signaling are also required for the development of vertebrate neural retina.This structure develops from a neuroepithelium composed of multipotent progenitors, which undergo a series of competence states to give rise to six neuronal and one glial cell types 2 . As progenitor cells produce the various cell types, Notch through lateral inhibition, maintains neighboring cells in a multipotent, proliferative state, ensuring that sufficient numbers of progenitors are retained for consecutive waves of neurogenesis. Thus, downregulation of Notch is a prerequisite for retinal neuronal differentiation 2 .Wnt/βcatenin signaling has also been implicated in the proliferation of vertebrate retinal precursors. However, in the mouse embryonic neural retina this function is limited to progenitor cells located in the periphery 3, 4 . In contrast, Wnt/βcatenin signaling is not active in the central retina and cell proliferation and differentiation proceed normally in mice with conditional deletion of βcatenin in the neural retina, although retinal lamination is altered 5 .Similarly, retinal specific inactivation of Fzd5, a non-canonical Wnt receptor mostly impacts on retinal vasculature formation but has no effect on neurogenesis 6 By analyzing the functional consequences of Sfrp1 and Sfrp2 compound inactivation during mouse retinal neurogenesis, we demonstrate here a novel and Wnt-independent role of Sfrps in the regulation of Notch signaling. We explain this finding by demonstrating that Sfrps can bind and downregulate the activity of ADAM10, a metalloprotease with multiple substrates including Notch, N-cadherin and APP. 4 RESULTS Sfrp1 and Sfrp2 are essential for proper eye developmentSfrp1 and Sfrp2 are expressed during murine eye development with a complementary pattern that includes all eye structures 7 . Sfrp1 transcripts are localized to the optic cup periphery and the retina pigmented epithelium from E10.5, while Sfrp2 is predominant in the neural retina (Fig. S1). Despite restricted mRNA expression, Sfrp proteins efficiently diffuse in the extracellular space 17 and Sfrp1 was immunodetected, albeit at low levels, also in the neural retina (Fig. S1), supporting the proposed Sfrp functional redundancy 9, 11, 12 .Accordingly, the eye of Sfrp1 and Sfrp2 single null embryos appeared histologically normal.In contrast at E16.5, the latest viable stage, the eyes of Sfrp1 -/-;Sfrp2 -/-compound mutants (n=20) were smaller than those of control littermates (n=30) with morphological visible alterations, including dorsal peripheral defects, reduction of the lens size, abnormal cornea and eye lid formation, increased thickness of the neural retina and abnormal vitreal accumulation of mesenchyme-derived angioblasts that normally form the hyaloid artery, the major vascular structure of the embryonic eye (Fig. S2). Inactivation of Sfrp1/2 alters retinal neurogenesisMultipotent progenitors in the neural retina generates neuronal and one glial cells wi...

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“…The Tissue Inhibitor of Metalloproteinases (TIMPs) demonstrate selectivity in their inhibition of ADAMs and ADAMTSs which contrasts with their MMP-inhibitory features [26][27][28][29]. For example, ADAM-17 is exclusively inhibited by TIMP-3, ADAM-10 is sensitive to TIMP-1 and TIMP-3, but not to TIMP-2 and TIMP-4.…”

Section: Structural Features Of Adams and Adamtssmentioning

confidence: 99%

Emerging roles of ADAM and ADAMTS metalloproteinases in cancer

et al. 2008

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A disintegrin and metalloproteinases (ADAMs) are a recently discovered family of proteins that share the metalloproteinase domain with matrix metalloproteinases (MMPs). Among this family, structural features distinguish the membrane-anchored ADAMs and the secreted ADAMs with thrombospondin motifs referred to as ADAMTSs. By acting on a large panel of membrane-associated and extracellular substrates, they control several cell functions such as adhesion, fusion, migration and proliferation. The current review addresses the contribution of these proteinases in the positive and negative regulation of cancer progression as mainly mediated by the regulation of growth factor activities and integrin functions.

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The in vitro activity of ADAM‐10 is inhibited by TIMP‐1 and TIMP‐3

Cited by 365 publications

References 26 publications

Collagen type I selectively activates ectodomain shedding of the discoidin domain receptor 1: Involvement of Src tyrosine kinase

Collagen type I selectively activates ectodomain shedding of the discoidin domain receptor 1: Involvement of Src tyrosine kinase

SFRPs act as negative modulators of ADAM10 to regulate retinal neurogenesis

Emerging roles of ADAM and ADAMTS metalloproteinases in cancer

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