TGF-β1 binding protein: A component of the large latent complex of TGF-β1 with multiple repeat sequences

Kanzaki, Tetsuto; Olofsson, Anders; Morén, Anita; Wernstedt, Christer; Hellman, Ulf; Miyazono, Kohei; Claesson‐Welsh, Lena; Heldin, Carl‐Henrik

doi:10.1016/0092-8674(90)90069-q

Cited by 435 publications

(324 citation statements)

References 37 publications

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“…11 TGF-b-LAP complex, also known as small latent TGF-b (SL-TGF-b), is further assembled into the large latent complex (LL-TGF-b) by the formation of the disulfide linkages between LAP and the latent-TGF-b-binding proteins (LTBPs). 12 LTBPs (LTBP-1, -3, and -4) confer efficient secretion and subsequent deposition of the latent TGF-bs to the extracellular matrix (ECM) due to the specific interactions of LTBPs with the ECM components. 10,13 Thus, the formation of B290 kDa LL-TGF-b complex (TGF-b, its propeptide LAP, and LTBP), anchored to the ECM, 14 (see also Figure 2) represents the predominant way of storage of the latent TGF-b.…”

Section: Introductionmentioning

confidence: 99%

Apoptosis of human endothelial cells is accompanied by proteolytic processing of latent TGF-β binding proteins and activation of TGF-β

Solovyan

Keski‐Oja

2005

Cell Death Differ

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Transforming growth factors b (TGF-bs) are multifunctional cytokines that modulate cell growth, differentiation and apoptosis. Numerous effects initiated by TGF-bs in vitro have been described, but the role of TGF-b targeting and activation under physiological conditions has gained very little attention and understanding. We report here that apoptosis of human umbilical vein endothelial cells (HUVECs) is accompanied by release of truncated large latent TGF-b complexes from the pericellular matrix followed by activation of TGF-b. The activation of TGF-b during apoptosis was accompanied by enhanced secretion of b1-LAP protein, and apoptotic HUVECs acquired the capacity to induce the release of latent TGF-bbinding proteins (LTBPs) from extracellular matrices. Activated TGF-b, in turn, attenuated apoptotic death of HUVECs. Current results indicate that the activation of TGF-b accompanies the apoptosis of HUVECs, and may play a protective feedback role against apoptotic cell death. The results suggest a role for TGF-b as a putative extracellular modulator of apoptosis.

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Section: Introductionmentioning

confidence: 99%

Apoptosis of human endothelial cells is accompanied by proteolytic processing of latent TGF-β binding proteins and activation of TGF-β

Solovyan

Keski‐Oja

2005

Cell Death Differ

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“…So far two members of this family, fibrillin-1 [3][4][5][6] and fibrillin-2 [4,7], have been described as products of different genes. These proteins share a common organization of domains consisting mostly of calcium-binding EGF-like repeats and novel motifs containing 8 cysteines, which are also found in the family of TGF-13 binding proteins [3,5,8]. Also common to both proteins is the presence of RGD sequences suggesting possible interactions with integrin adhesion receptors [9].…”

Section: Introductionmentioning

confidence: 99%

Cell adhesion and integrin binding to recombinant human fibrillin‐1

et al. 1996

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Fibrillin-1 is a major constituent of tissue microfibrfls that occur in most connective tissues, either in close association with or independent of elastin. To test possible cell-adhesive functions of this protein, we used recombinant human fibrlllin-1 polypeptides produced in a mammalian expression system in cell attachment and solid-phase integrin binding assays. necessitates the use of buffers containing denaturing agents and cannot separate fibrillin-1 and fibrillin-2 [18], we chose to use recombinant human fibrillin-1 polypeptides for a study of possible cell-adhesive functions. These human fibrillin-1 peptides were produced in a mammalian expression system and purified under non-denaturing conditions [19]. Extensive characterization indicated correct folding [19]. Using an experimental approach already applied to characterize cell-adhesive and integrin-binding functions of fibulins [20], laminin [21] and collagen VI [22], we demonstrate the ability of cells to adhere to fibrillin-1 via an RGD motif located in the fourth 8-cysteine domain. In addition we identify integrin aV[33 as a major cellular receptor for this site.

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“…This mechanism for the initiation of a biological response has been observed in the regulation of other bioactive molecules such as clotting factors. In fact, some of the sequence motifs (e.g., kringle and epidermal growth factor-like repeats) present in surface-activatible clotting factors are also present in growth factors and their binding proteins (e.g., hepatocyte growth factor and the binding protein of latent transforming growth factor-f1) (Kanzaki et al, 1990;Tashiro et al, 1990). The availability of the reactants that catalyze the release of the active growth factor also effects the duration of growth factor activity because new factor will only be produced in the presence of the activating molecules.…”

Section: Regulation In Time and Spacementioning

confidence: 99%

“…The latent TGF-f binding protein (LTBP) contains 16 EGFlike repeats, an RGD sequence, and a laminin B2 sequence (Kanzaki et al, 1990); motifs previously shown to be involved in protein-protein interactions (Ruoslahti and Pierschbacher, 1987;Sasaki and Yamada, 1987;Appella et al, 1988). LTBP has been shown to participate in the activation of latent TGF-,B1 (Flaumenhaft et al., unpublished data) and might serve to direct the latent high molecular weight TGF-,31 to a cell surface site where mature TGF-,B1 is released from the latent complex via proteolysis .…”

Section: Regulation In Time and Spacementioning

confidence: 99%