The Transforming Growth Factor-β-inducible Matrix Protein βig-h3 Interacts with Fibronectin

Abstract

Proper growth and development require the orderly synthesis and deposition of individual components of the extracellular matrix (ECM) into well ordered networks. Once formed, the ECM maintains tissue structure and houses resident cells. One ECM component, ␤ig-h3, is a highly conserved transforming growth factor-␤-inducible protein that has been hypothesized to function as a bifunctional linker between individual matrix components and resident cells. To gain insights into its physiological function, full-length ␤ig-h3 protein was produced using a baculovirus expression system and purified under native conditions. Human fibroblasts attached and spread on ␤ig-h3-coated plates and developed actin stress fibers. Purified ␤ig-h3 binds fibronectin (FN) and type I collagen (Col I) but does not bind gelatin. Using defined fragments of FN, we localized the ␤ig-h3 recognition region to the gelatin/collagen binding domain present in the N-terminal region of the FN molecule. Our results identify FN and Col I as two ligands of ␤ig-h3 in the ECM.

Comparative Proteomic Analysis of Normal and Collagen IX Null Mouse Cartilage Reveals Altered Extracellular Matrix Composition and Novel Components of the Collagen IX Interactome

“…Tgfbi is attached at periodic intervals with collagen VI microfibrils extracted under native conditions (18) and Tgfbi⅐biglycan complexes enhance the formation of collagen VI networks in vitro (54), supporting a role for Tgfbi in matrix organization. In addition, Tgfbi interacts with fibronectin and is thought to facilitate cell-matrix interactions via an integrin-binding RGD motif (55). Validation of our proteomics analysis by Western blotting confirmed that fibronectin and Tgfbi, both of which are TGF␤-regulated proteins, were expressed at elevated levels in collagen IX null cartilage but were unaffected in COMP null cartilage.…”

Periostin promotes invasiveness and resistance of pancreatic cancer cells to hypoxia-induced cell death: role of the β4 integrin and the PI3k pathway

“…While one report demonstrated that ectopic expression of periostin enhanced metastatic growth of colon cancer by preventing stress-induced apoptosis in cancer another showed evidence for a potential tumour suppressor function as overexpression of periostin suppressed the invasiveness and metastasis of tumour cells (Kim et al, 2005). Furthermore, the exact mechanism by which periostin exerts its biological function has remained elusive as in all cancer types tested to date periostin was reported to be localised in the cytoplasm of tumour cells and never in the surrounding stroma, which is surprising for a typically secreted protein sharing significant homology with the big-h3 protein (Gibson et al, 1997;Billings et al, 2002).…”

Association of TCF4 and CLU polymorphisms with Fuchs’ endothelial dystrophy and implication of CLU and TGFBI proteins in the disease process

“…TGFBI mediates cell adhesion by interacting with collagens, fibronectin and integrins, which are major components of the DM. 43,44 TGF-b, which induces the TGFBI protein, has a reported role in the regulation of TCF4 and ZEB1 through signaling pathways in EMT. 26 Mutations in TGFBI cause some human corneal dystrophies, but have not been reported to cause FED.…”