TGF-beta1 binding protein-like modules of fibrillin-1 and -2 mediate integrin-dependent cell adhesion.
Human fibrillin, a major component of the extracellular matrix, exists as two highly homologous forms (fibrillin-1 and -2). Several modules of fibrillin are homologous to TGF-beta1 binding protein. Two of these modules, D25 (the 25th module of fibrillin-1 and -2 D segment) and D12 (the 12th module of fibrillin-2 D segment) contain the cell adhesion motif arginyl-glycyl-aspartyl (RGD). The ability of RGD to mediate adhesion to D25-1 and D12-2 was investigated using bacterially expressed fusion proteins. Human skin fibroblasts and murine L-cells were used in microassays of cell attachment and cell spreading on fibrillin fusion-protein substrata. Dose-dependent experiments and competitive inhibition by soluble RGD-containing peptides demonstrated that D25-1 and D12-2 mediate RGD-dependent cell adhesion. These results provide evidence for a cell adhesion function of fibrillin-2. Inhibition with anti-integrin antibodies showed that alpha(v) and beta3 integrins mediate adhesion to D25-1, while alpha3, alpha(v) and beta1 are involved in adhesion to D12-2. Binding of different receptors may elicit distinct cell signalling supporting the hypothesis that fibrillin-1 and fibrillin-2 have distinct roles.
D'Arrigo
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Department of Neuropathology, Institute of Neurology, London, UK.
Burl
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Withers
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Dobson
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Black
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Boxer
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D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects; D003094:Collagen / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects; D000071838:Fibrillin-1; D000071840:Fibrillin-2; D000071837:Fibrillins; D005353:Fibronectins / Q000494:pharmacology; D006801:Humans; D016023:Integrins / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins; D007739:L Cells; D053779:Latent TGF-beta Binding Proteins; D051379:Mice; D008840:Microfilament Proteins / Q000502:physiology*; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D017386:Sequence Homology, Amino Acid; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D054392:Adipokines
D002352:Carrier Proteins; D003094:Collagen; D000071838:Fibrillin-1; D000071840:Fibrillin-2; D000071837:Fibrillins; D005353:Fibronectins; D016023:Integrins; D047908:Intracellular Signaling Peptides and Proteins; D053779:Latent TGF-beta Binding Proteins; D008840:Microfilament Proteins; D010455:Peptides; D012710:Serum Albumin, Bovine; C000605722:FBN1 protein, human; D054392:Adipokines; C000605723:FBN2 protein, human; C000605724:Fbn1 protein, mouse; C000605728:Fbn2 protein, mouse