Integrin α4β1-Dependent Adhesion to ADAM 28 (MDC-L) Requires an Extended Surface of the Disintegrin Domain

Bridges, Lance C.; Hanson, Krista; Tani, P; Mather, Timothy; Bowditch, Ron D.

doi:10.1021/bi026871y

Cited by 31 publications

(26 citation statements)

References 49 publications

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“…ADAM28 may also be involved in activation of EGFR, MAPK1, MAPK3, and release of CD44, with a possible role in the in the proliferation of lung cancer cell line NCI-H292 (Hart S et al, 2004). In addition, ADAM28 has been shown to interact with integrins and is involved in the digestion of IGFBP3 through release of IGF1, a potent inducer of cell proliferation (Bridges et al, 2003;Mochizuki et al, 2004). This digestion has been shown to be inhibited by TIMP3 and TIMP4 (tissue inhibitors of metalloproteinases).…”

Section: Discussionmentioning

confidence: 99%

ADAM28: A potential oncogene involved in asbestos‐related lung adenocarcinomas

Wright

Larsen

Hayward

et al. 2010

Genes Chromosomes & Cancer

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Asbestos-related lung cancer accounts for 4-12% of all lung cancers worldwide. Since putative mechanisms of carcinogenesis differ between asbestos and tobacco induced lung cancers, tumors induced by the two agents may be genetically distinct. To identify gene expression biomarkers associated with asbestos-related lung tumorigenicity we performed gene expression array analysis on tumors of 36 patients with primary lung adenocarcinoma, comparing 12 patients with lung asbestos body counts above levels associated with urban dwelling (ARLC-AC: asbestos-related lung cancer-adenocarcinoma) with 24 patients with no asbestos bodies (NARLC-AC: non-asbestos related lung cancer-adenocarcinoma). Genes differentially expressed between ARLC-AC and NARLC-AC were identified on fold change and P value, and then prioritized using gene ontology. Candidates included ZNRF3, ADAM28, PPP1CA, IRF6, RAB3D, and PRDX1. Expression of these six genes was technically and biologically replicated by qRT-PCR in the training set and biologically validated in three independent test sets. ADAM28, encoding a disintegrin and metalloproteinase domain protein that interacts with integrins, was consistently upregulated in ARLC across all four datasets. Further studies are being designed to investigate the possible role of this gene in asbestos lung tumorigenicity, its potential utility as a marker of asbestos related lung cancer for purposes of causal attribution, and its potential as a treatment target for lung cancers arising in asbestos exposed persons.

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Section: Discussionmentioning

confidence: 99%

ADAM28: A potential oncogene involved in asbestos‐related lung adenocarcinomas

Wright

Larsen

Hayward

et al. 2010

Genes Chromosomes & Cancer

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“…An extensive molecular surface of the elongated arm structure (12 000 Å 2 for the VAP1 D/C-domains) might reveal additional protein-protein interaction interfaces other than the HVR. Multiple charged residues in the D-domain are essential for ADAM28 binding to a4b1 (Bridges et al, 2003) and the RX 6 DLPEF motif has been proposed for integrin a9b1 binding (Eto et al, 2002). However, the D-domain portion of the C-shaped scaffold is away from the catalytic site; thus, those additional sites might not directly serve as target recognition interfaces for catalysis.…”

Section: Discussionmentioning

confidence: 99%

Crystal structures of VAP1 reveal ADAMs' MDC domain architecture and its unique C-shaped scaffold

Takeda

Igarashi

Mori

et al. 2006

EMBO J

185

190

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ADAMs (a disintegrin and metalloproteinase) are sheddases possessing extracellular metalloproteinase/disintegrin/cysteine-rich (MDC) domains. ADAMs uniquely display both proteolytic and adhesive activities on the cell surface, however, most of their physiological targets and adhesion mechanisms remain unclear. Here for the first time, we reveal the ADAMs' MDC architecture and a potential target-binding site by solving crystal structures of VAP1, a snake venom homolog of mammalian ADAMs. The D-domain protrudes from the M-domain opposing the catalytic site and constituting a C-shaped arm with cores of Ca 2 þ ions. The disintegrin-loop, supposed to interact with integrins, is packed by the C-domain and inaccessible for protein binding. Instead, the hyper-variable region (HVR) in the C-domain, which has a novel fold stabilized by the strictly conserved disulfide bridges, constitutes a potential protein-protein adhesive interface. The HVR is located at the distal end of the arm and faces toward the catalytic site. The C-shaped structure implies interplay between the ADAMs' proteolytic and adhesive domains and suggests a molecular mechanism for ADAMs' target recognition for shedding.

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“…Most ADAMs such as ADAM9, -12, -15, -19, and -28 interact with several integrins, mainly ␣4␤1 and/or ␣9␤1 (15,40), and this interaction is generally thought to occur through binding between integrins and the integrin-binding motif (RX 6 DLPEF), called the disintegrin-loop, in the Dis domains of most ADAM species (41). However, residues located outside of the disintegrin loop are also known to participate in integrin recognition of ADAM28 (42). In addition, a recent study on the crystal structure has demonstrated that the disintegrin-loop is packed against the CR domain and stabilized by a disulfide bridge within the Dis domain and suggested that the loop of membrane-anchored ADAM is inaccessible for other proteins (16).…”

Section: Discussionmentioning

confidence: 99%

Binding of ADAM28 to P-selectin Glycoprotein Ligand-1 Enhances P-selectin-mediated Leukocyte Adhesion to Endothelial Cells

Shimoda

Hashimoto

Mochizuki

et al. 2007

Journal of Biological Chemistry

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A disintegrin and metalloproteinases (ADAMs)2 are a recently discovered gene family of membrane-anchored and secreted proteins that have proteolytic and/or adhesive properties (1, 2). At present, more than 30 members have been identified in humans (3, 4). The precursor forms of ADAMs (proADAMs) are composed of propeptide, metalloproteinase, disintegrin-like, cysteine-rich, epidermal growth factor (EGF)-like, transmembrane and cytoplasmic domains (4, 5). Roles of ADAMs include cell surface processing of membrane proteins such as tumor necrosis factor-␣ by ADAM17 (6), heparin-binding epidermal growth factor by ADAM9 (7), ADAM12 (8), and ADAM17 (9) and amyloid precursor protein by ADAM10 (10) and ADAM17 (11). ADAMs are also reported to digest various proteins, including type IV collagen by ADAM10 (12) and insulin-like growth factor binding protein-3 (IGFBP-3) by ADAM12 (13) and ADAM28 (14). On the other hand, accumulated lines of evidence have shown that the disintegrin-like domain of many ADAM members interacts with integrins (3, 15), although a recent study on crystal structures suggested that the integrin-binding motif within the disintegrin-like domain is structurally inaccessible for protein binding (16). The secreted form of ADAM9 has recently been reported to lead to invasion by binding to ␣6␤4 and ␣2␤1 integrins (17). The cysteine-rich domain of ADAM12 is known to interact with syndecans on mesenchymal cells, leading to the ␤1 integrin-mediated cell spreading (18). The disintegrin-like and cysteine-rich domains of ADAM13 bind to laminin and fibronectin (19). However, information about the binding molecules of ADAMs and their functional modulation by these interactions is still limited.ADAM28 is expressed by human peripheral blood lymphocytes in two alternative forms, i.e. a prototype membrane-anchored form (ADAM28m) and a secreted form (ADAM28s) (20). The disintegrin-like domain of ADAM28 is reported to interact with integrins ␣4␤1, ␣4␤7 and ␣9␤1 on lymphocytes in an activation-dependent manner of the integrins (21, 22). The metalloproteinase domain of ADAM28 has the zinc-binding catalytic-site consensus sequence, and ADAM28 cleaves myelin basic protein (23), CD23 ectodomain (24), and . In addition, we have reported that ADAM28 is overexpressed in non-small cell lung carcinomas with correlations to carcinoma cell proliferation and lymph node metastasis (25), and we have recently shown that ADAM28 plays a role in breast carcinoma cell proliferation through enhanced bioavailability of insulinlike growth factor-I by selective digestion of IGFBP-3 of the insulin-like growth factor-I⅐IGFBP-3 complex (26). Thus, these data suggest the possibility that ADAM28 is involved in various cellular and tissue reactions such as cell-cell and cell-matrix interactions, cell motility, shedding of cell surface proteins, and * This work was supported by Grants-in-aid for Scientific Research 16209015 and 18790254 from the Japanese Ministry of Education, Culture, Sports, Science, and Technology (to Y. O. and M. S., respectively)....

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Integrin α4β1-Dependent Adhesion to ADAM 28 (MDC-L) Requires an Extended Surface of the Disintegrin Domain

Cited by 31 publications

References 49 publications

ADAM28: A potential oncogene involved in asbestos‐related lung adenocarcinomas

ADAM28: A potential oncogene involved in asbestos‐related lung adenocarcinomas

Crystal structures of VAP1 reveal ADAMs' MDC domain architecture and its unique C-shaped scaffold

Binding of ADAM28 to P-selectin Glycoprotein Ligand-1 Enhances P-selectin-mediated Leukocyte Adhesion to Endothelial Cells

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