Abstract
Transforming growth factor-betas (TGF-beta) are secreted as latent complexes consisting of the TGF-beta dimer, the TGF-beta propeptide dimer, and the latent TGF-beta binding protein (LTBP). Although the bonds between TGF-beta and its propeptide are cleaved intracellulary, the propeptide associates with TGF-beta by electrostatic interactions, thereby conferring latency to the complex. We reported that a specific sequence of LTBP-1 is required for latent TGF-beta activation by the integrin alphavbeta6. Here we describe a 24 amino acid sequence from the hinge domain required for activation. The LTBP-1 polypeptide rL1N, which includes the hinge, associates with fibronectin in binding assays. We present evidence that fibronectin null cells minimally activate latent TGF-beta and poorly incorporate the active hinge sequence into their matrix. In addition, cells missing the fibronectin receptor alpha5beta1 exhibit defective activation of latent TGF-beta by alphavbeta6 and decreased matrix incorporation. The results indicate specificity for integrin-mediated latent TGF-beta activation that include unique sequences in LTBP-1 and an appropriate matrix molecule.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Antigens, Neoplasm / chemistry*
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Antigens, Neoplasm / metabolism
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Biological Assay
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Blotting, Western
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CHO Cells
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Collodion / chemistry
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Cricetinae
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Dimerization
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Electrophoresis, Polyacrylamide Gel
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Epitopes / chemistry
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Fibronectins / chemistry
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Fibronectins / physiology*
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Genetic Vectors
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Integrins / chemistry*
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Integrins / metabolism
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Intracellular Signaling Peptides and Proteins / chemistry*
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Intracellular Signaling Peptides and Proteins / metabolism
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Latent TGF-beta Binding Proteins
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Luciferases / metabolism
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Mice
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Microscopy, Fluorescence
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Molecular Sequence Data
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Peptides / chemistry
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Protein Binding
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Protein Structure, Tertiary
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RNA, Messenger / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Time Factors
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Transforming Growth Factor beta / metabolism*
Substances
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Antigens, Neoplasm
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Epitopes
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Fibronectins
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Integrins
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Intracellular Signaling Peptides and Proteins
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Latent TGF-beta Binding Proteins
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Ltbp1 protein, mouse
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Peptides
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RNA, Messenger
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Transforming Growth Factor beta
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integrin alphavbeta6
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Collodion
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Luciferases