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Identification of the growth factor-binding sequence in the extracellular matrix protein MAGP-1.

ABSTRACT: Microfibril-associated glycoprotein-1 (MAGP-1) is a component of vertebrate extracellular matrix (ECM) microfibrils that, together with the fibrillins, contributes to microfibril function. Many of the phenotypes associated with MAGP-1 gene inactivation are consistent with dysregulation of the transforming growth factor ? (TGF?)/bone morphogenetic protein (BMP) signaling system. We have previously shown that full-length MAGP-1 binds active TGF?-1 and some BMPs. The work presented here further defines the growth factor-binding domain of MAGP-1. Using recombinant domains and synthetic peptides, along with surface plasmon resonance analysis to measure the kinetics of the MAGP-1-TGF?-1 interaction, we localized the TGF?- and BMP-binding site in MAGP-1 to a 19-amino acid-long, highly acidic sequence near the N terminus. This domain was specific for binding active, but not latent, TGF?-1. Growth factor activity experiments revealed that TGF?-1 retains signaling activity when complexed with MAGP-1. Furthermore, when bound to fibrillin, MAGP-1 retained the ability to interact with TGF?-1, and active TGF?-1 did not bind fibrillin in the absence of MAGP-1. The absence of MAGP was sufficient to raise the amount of total TGF? stored in the ECM of cultured cells, suggesting that the MAGPs compete with the TGF? large latent complex for binding to microfibrils. Together, these results indicate that MAGP-1 plays an active role in TGF? signaling in the ECM.

SUBMITTER: Broekelmann TJ

PROVIDER: S-EPMC7049978 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Identification of the growth factor-binding sequence in the extracellular matrix protein MAGP-1.

Broekelmann Thomas J TJ Bodmer Nicholas K NK Mecham Robert P RP

The Journal of biological chemistry 20200127 9

Microfibril-associated glycoprotein-1 (MAGP-1) is a component of vertebrate extracellular matrix (ECM) microfibrils that, together with the fibrillins, contributes to microfibril function. Many of the phenotypes associated with <i>MAGP-1</i> gene inactivation are consistent with dysregulation of the transforming growth factor β (TGFβ)/bone morphogenetic protein (BMP) signaling system. We have previously shown that full-length MAGP-1 binds active TGFβ-1 and some BMPs. The work presented here furt ...[more]

PMID: 31988245

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Dataset Information

Identification of the growth factor-binding sequence in the extracellular matrix protein MAGP-1.

Publications

Identification of the growth factor-binding sequence in the extracellular matrix protein MAGP-1.

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