Physiology of Thrombospondin

Mosher, Deane F.

doi:10.1146/annurev.me.41.020190.000505

Cited by 177 publications

(85 citation statements)

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“…They suggested that thrombospondin 1 may function by priming cells for mitosis by inhibiting the formation of focal adhesion plaques. This is supported by findings that thrombospondin 1 is involved in the mechanisms of cellular proliferation [12,25]. The functions of thrombospondin 1 in normal and pathological articular and meniscal cartilage remain to be established.…”

Section: Discussionmentioning

confidence: 74%

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Thrombospondin 1 binds to the surface of bovine articular chondrocytes by a linear RGD‐dependent mechanism

Miller

McDevitt

1995

FEBS Letters

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Thrombospondin 1 is present in articular cartilage and is synthesized by chondrocytes. Adult bovine articular chondrocytes in serum-free medium were evaluated in a solid-phase assay for their ability to attach to thrombospondin 1 isolated from human platelets. The chondrocytes attached to the thrombospondiu 1 by a mechanism that was inhibited by a synthetic linear GRGDSP but not a GRGESP peptide. The cells, however, did not spread on thrombospondiu 1, but did spread on fibrouectin and Pep-Tite 2000, a synthetic RGD-containing peptide. Preincubation of thrombospondin 1 with EDTA irreversibly inhibited its capacity to attach to chondrocytes. We conclude that thrombospondin 1 binds to chondrocytes by its RGD sequence.

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Section: Discussionmentioning

confidence: 74%

“…The RGD sequence in a variety of adhesive proteins often mediates their interaction with specific members of the integrin family of receptors [10]. Although thrombospondin 1 promotes cell attachment in both normal and transformed cells [11,12], some of these interactions are not *Corresponding author. Fax: (1) (216) 444 9198.…”

Section: Introductionmentioning

confidence: 99%

Thrombospondin 1 binds to the surface of bovine articular chondrocytes by a linear RGD‐dependent mechanism

Miller

McDevitt

1995

FEBS Letters

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“…Normally only present in very low quantities in plasma (1,2), upon blood coagulation and activation of platelets, TSP1 is released into serum and is incorporated into fibrin clots (3,4). TSP1 is composed of three identical 150-kDa monomers connected by disulfide bridges (5).…”

Section: Thrombospondin 1 (Tsp1)mentioning

confidence: 99%

“…Functions of TSP1 include cell adhesion (6), inhibition of angiogenesis and endothelial cell proliferation (7), and activation of latent transforming growth factor-␤ (TGF-␤) (8). The different modules mediate binding of TSP1 to cells, platelets, and numerous proteins such as collagen, fibronectin, heparan sulfate proteoglycan, laminin, fibrinogen, plasminogen, and histidine-rich glycoprotein (1,2). Many of the interactions are mediated by N, which contains a heparin-binding site (9 -11).…”

Section: Thrombospondin 1 (Tsp1)mentioning

confidence: 99%

Physical Characterization of the Procollagen Module of Human Thrombospondin 1 Expressed in Insect Cells

Misenheimer

Huwiler

Annis

et al. 2000

Journal of Biological Chemistry

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Thrombospondin 1 (TSP1) is a homotrimeric glycoprotein composed of 150-kDa subunits connected by disulfide bridges. The procollagen module of thrombospondin 1 has been implicated in antiangiogenic activity. Procollagen modules are found in a number of extracellular proteins and are identifiable by 10 cysteines with characteristic spacing. We expressed and studied the procollagen module (C) of human TSP1, both by itself and in the context of the adjoining oligomerization sequence (o) and N-terminal module (N). The coding sequences were introduced into baculoviruses along with an N-terminal signal sequence and C-terminal polyhistidine tag. Proteins were purified from conditioned medium of infected insect cells by nickel-chelate chromatography. NoC is a disulfide bonded trimer and cleaves readily at a site of preferential proteolysis to yield monomeric N and trimeric oC. These are known properties of full-length TSP1. Mass spectroscopy indicated that C is N-glycosylated, and all 10 cysteine residues of C are in disulfides. By equilibrium ultracentrifugation, C is a monomer in physiological salt solution. Circular dichroism, intrinsic fluorescence, and differential scanning calorimetry experiments suggest that the stability of C is determined by the disulfides. The two tryptophans of C are in a polar, exposed environment as assessed by iodide fluorescence quenching and solvent perturbation. The oC far UV circular dichroism spectrum could be modeled as the sum of C and a coiled-coil oligomerization domain. The results indicate that the recombinant C folds autonomously into its native structure, and trimerization of the modules in TSP1 does not perturb their structures.

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“…It is stored within secretory granules of platelets (11,12) and is the major protein released from these cells when they are stimulated with agonists (11)(12)(13). Although a variety of functions have been ascribed to TSP-1 and its domains (14,15), the region harboring the N700S SNP is devoid of such known functional assignments with respect to platelet and other vascular cell responses (14,16). Moreover, TSP-1 has not been previously regarded as a significant contributor to thrombotic diseases.…”

mentioning

confidence: 99%

Molecular and Functional Differences Induced in Thrombospondin-1 by the Single Nucleotide Polymorphism Associated with the Risk of Premature, Familial Myocardial Infarction

Narizhneva

Byers-Ward

Quinn

et al. 2004

Journal of Biological Chemistry

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A serine (Ser-700) amino acid rather than an asparagine (Asn-700) at residue 700 of thrombospondin-1 has been linked to an increased risk for development of premature, familial heart attacks. We now have identified both functional and structural differences between the Ser-700 and Asn-700 thrombospondin-1 variants. The Ser-700 variant increased the rate and extent of platelet aggregation and showed increased surface expression on platelets compared with the Asn-700 variant. These differences could be ascribed to an enhanced interaction of the Ser-700 variant with fibrinogen on the platelet surface and are consistent with a prothrombotic phenotype in Ser-700 individuals. The Ser-700 variant thrombospondin-1 was conformationally more labile than the Asn-700 variant as demonstrated by increased susceptibility to proteolytic digestion and enhanced susceptibility to unfolding by denaturants. These data suggest a potential molecular and cellular basis for a genetic risk factor associated with early onset myocardial infarction.

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Physiology of Thrombospondin

Cited by 177 publications

References 0 publications

Thrombospondin 1 binds to the surface of bovine articular chondrocytes by a linear RGD‐dependent mechanism

Thrombospondin 1 binds to the surface of bovine articular chondrocytes by a linear RGD‐dependent mechanism

Physical Characterization of the Procollagen Module of Human Thrombospondin 1 Expressed in Insect Cells

Molecular and Functional Differences Induced in Thrombospondin-1 by the Single Nucleotide Polymorphism Associated with the Risk of Premature, Familial Myocardial Infarction

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