LTBP-2 specifically interacts with the amino-terminal region of fibrillin-1 and competes with LTBP-1 for binding to this microfibrillar protein

Hirani, Rena; Hanssen, Eric; Gibson, Mark

doi:10.1016/j.matbio.2006.12.006

Cited by 121 publications

(125 citation statements)

References 48 publications

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“…The N-terminal end of LTBP-2 was found to bind to fibulin-5 (42), and the C-terminal end of LTBP-2 interacted with fibrillin-1 (41). In our studies, the C-terminal ends of LTBP-1 and LTBP-4 interacted with fibrillin-1, but not to fibulins.…”

Section: Discussionsupporting

confidence: 45%

Latent Transforming Growth Factor β-binding Proteins and Fibulins Compete for Fibrillin-1 and Exhibit Exquisite Specificities in Binding Sites

Ono

Sengle

Charbonneau

et al. 2009

Journal of Biological Chemistry

153

196

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Latent transforming growth factor (TGF)␤Results demonstrate that these protein-protein interactions exhibit "exquisite specificities," a phrase commonly used to describe monoclonal antibody interactions. Despite these differences, interactions between LTBP-1 and fibrillin-1 compete for interactions between fibrillin-1 and these fibulins. All of these proteins have been immunolocalized to microfibrils. However, in fibrillin-1 (Fbn1) null fibroblast cultures, LTBP-1 and LTBP-4 are not incorporated into microfibrils. In contrast, in fibulin-2 (Fbln2) null or fibulin-4 (Fbln4) null cultures, fibrillin-1, LTBP-1, and LTBP-4 are incorporated into microfibrils. These data show for the first time that fibrillin-1, but not fibulin-2 or fibulin-4, is required for appropriate matrix assembly of LTBPs. These studies also suggest that the fibulins may affect matrix sequestration of LTBPs, because in vitro interactions between these proteins are competitive.

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Section: Discussionsupporting

confidence: 45%

Latent Transforming Growth Factor β-binding Proteins and Fibulins Compete for Fibrillin-1 and Exhibit Exquisite Specificities in Binding Sites

Ono

Sengle

Charbonneau

et al. 2009

Journal of Biological Chemistry

153

196

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“…Fibrillin-1 deposition, which has been reported to be dependent on fibronectin assembly, was accordingly rescued under the same conditions. LTBP-2 temporally colocalizes with fibrillin-1 LTBP-2 binds to fibrillin-1 but not to fibrillin-2 (Hirani et al, 2007). LTBP-2 and fibrillin-1 also colocalize in human aorta.…”

Section: Ltbp-2 Fails To Assemble To the Extracellular Matrix Of Fnà/mentioning

confidence: 95%

“…Studies utilizing recombinantly expressed LTBP-2 have implicated a role for it in the modulation of cell adhesion Vehviläinen et al, 2003). LTBP-2 was recently found to bind fibrillin-1 and to colocalize with it in human embryonic aorta (Hirani et al, 2007). Moreover, LTBP-2 was observed to regulate elastic fiber assembly through binding to DANCE/fibulin-5 and consequently promoting its deposition on fibrillin-1 molecules in human skin fibroblast culture (Hirai et al, 2007).…”

mentioning

confidence: 99%

Matrix association of latent TGF‐beta binding protein‐2 (LTBP‐2) is dependent on fibrillin‐1

Vehviläinen

Hyytiäinen

Keski‐Oja

2009

Journal Cellular Physiology

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The components of the extracellular matrix (ECM) and their differential expression patterns play important roles in tissue formation. The deposition of latent TGF-beta binding proteins (LTBPs) to the ECM exhibit distinct distribution profiles. We have analyzed here the temporal and spatial ECM association of latent TGF-beta binding protein LTBP-2 in cultured human embryonic lung fibroblasts. We found that LTBP-2 was not assembled to the ECM until by confluency of cultures following the deposition of fibronectin (FN) and fibrillin-1. In 5-day-old cultures LTBP-2 was rapidly secreted from cells and it subsequently associated with the ECM as shown by metabolic labeling and immunoprecipitation. LTBP-2 colocalized transiently with fibronectin and failed to assemble to the ECM of FN deficient mouse fibroblasts. Analysis of different cultured human cell lines revealed partial colocalization of LTBP-2 and fibrillin-1 in the ECM of fibroblasts, MG-63 osteosarcoma cells and human vascular endothelial cells. Silencing of fibrillin-1 expression by lentiviral shRNAs profoundly disrupted the deposition of LTBP-2. Current results suggest that LTBP-2 is not an element of the provisional ECM of fibroblasts but is more likely a component of more mature ECM and indicate that matrix association of LTBP-2 depends on a pre-formed fibrillin-1 network.

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“…LTBP2 does not bind any of the TGFb/LAP complexes, but it does bind microfibrils where it may play a structural role or participate in formation of microfibril-associated protein complexes by competing with other LTBPs for binding to fibrillin-1. 24,25 LTBP1 and LTBP3 bind all 3 TGFb/LAP complexes with equal affinity while LTBP4 weakly binds TGFb1/LAP. 18,25 Microfibrils regulate activation of TGFb, which involves release of LAP to allow interaction of the active TGFb with its receptor.…”

Section: Microfibrils Control Location and Activation Of Tgfbmentioning

confidence: 99%

The Microfibril Hypothesis of Glaucoma: Implications for Treatment of Elevated Intraocular Pressure

Kuchtey

2014

Journal of Ocular Pharmacology and Therapeutics

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Microfibrils are macromolecular aggregates located in the extracellular matrix of both elastic and nonelastic tissues that have essential functions in formation of elastic fibers and control of signaling through the transforming growth factor beta (TGFb) family of cytokines. Elevation of systemic TGFb and chronic activation of TGFb signal transduction are associated with diseases caused by mutations in microfibril-associated genes, including FBN1. A role for microfibrils in glaucoma is suggested by identification of risk alleles in LOXL1 for exfoliation glaucoma and mutations in LTBP2 for primary congenital glaucoma, both of which are microfibrilassociated genes.

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LTBP-2 specifically interacts with the amino-terminal region of fibrillin-1 and competes with LTBP-1 for binding to this microfibrillar protein

Cited by 121 publications

References 48 publications

Latent Transforming Growth Factor β-binding Proteins and Fibulins Compete for Fibrillin-1 and Exhibit Exquisite Specificities in Binding Sites

Latent Transforming Growth Factor β-binding Proteins and Fibulins Compete for Fibrillin-1 and Exhibit Exquisite Specificities in Binding Sites

Matrix association of latent TGF‐beta binding protein‐2 (LTBP‐2) is dependent on fibrillin‐1

The Microfibril Hypothesis of Glaucoma: Implications for Treatment of Elevated Intraocular Pressure

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