Thrombospondin II: Partial cDNA sequence, chromosome location, and expression of a second member of the thrombospondin gene family in humans

Labell, Terry L.; Milewicz, Dianna J. McGookey; Distèche, Christine M.; Byers, Peter H.

doi:10.1016/0888-7543(92)90430-z

Cited by 46 publications

(19 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Peak 6Ј was found only in Ca2 tun. The observed masses are those found in digests of Ca2 tun (peak 6Ј) or E3CaG2 (peaks [1][2][3][4][5][6] lar protein that has been found to contain a pair of EF-hand Ca 2ϩ -binding sites in which a disulfide bond is present to stabilize the loop (41), but the disulfide bond is between the E and F helices that are not present in E3CaG2.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Disulfide Connectivity of Recombinant C-terminal Region of Human Thrombospondin 2

Misenheimer

Hahr

Harms

et al. 2001

Journal of Biological Chemistry

View full text Add to dashboard Cite

The thrombospondin (TSP) family of extracellular glycoproteins consists of five members in vertebrates, TSP1 to -4 and TSP5/cartilage oligomeric matrix protein, and a single member in Drosophila. TSPs are modular multimeric proteins. The C-terminal end of a monomer consists of 3-6 EGF-like modules; seven tandem 23-, 36-, or 38-residue aspartate-rich, Ca 2؉ -binding repeats; and an ϳ230-residue C-terminal sequence. The Ca 2؉ -binding repeats and C-terminal sequence are spaced almost exactly the same in different TSPs and share many blocks of identical residues. We studied the C-terminal portion of human TSP2 from the third EGF-like module through the end of the protein (E3CaG2). E3CaG2, CaG2 lacking the EGF module, and Ca2 composed of only the Ca 2؉ -binding repeats were expressed using recombinant baculoviruses and purified from conditioned media of insect cells. As previously described for intact TSP1, E3CaG2 bound Ca 2؉ in a cooperative manner as assessed by equilibrium dialysis, and its circular dichroism spectrum was sensitive to the presence of Ca 2؉ . Mass spectrometry of the recombinant proteins digested with endoproteinase Asp-N revealed that disulfide pairing of the 18 cysteines in the Ca 2؉ -binding repeats and C-terminal sequence is sequential, i.e. a 1-2, 3-4, 5-6, etc., pattern.

show abstract

Section: Discussionmentioning

confidence: 99%

“…The thrombospondin (TSP) 1 family of extracellular glycoproteins consists of five members in vertebrates, TSP1-4 and TSP5/cartilage oligomeric matrix protein (COMP) (1)(2)(3)(4)(5), and a single member in Drosophila, dTSP (6,7). The temporal and spatial expression pattern of the TSP family members in vertebrates is distinctive (8 -10).…”

mentioning

confidence: 99%

Disulfide Connectivity of Recombinant C-terminal Region of Human Thrombospondin 2

Misenheimer

Hahr

Harms

et al. 2001

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Many of the functions attributed to TSP, as well as the receptorbinding sites, have been mapped to specific regions within these domains. Although these discrete domains, and the existence of several receptors, could account for the variety of functions attributed to TSP, reports of two additional homologous genes (TSP 2 and TSP 3) (Bornstein et al, 1991a,b;Lawler et al, 1991;LaBell et al, 1992;Vos et al, 1992;Laherty et al, 1992) have revealed a new dimension of complexity in the structure/function relationship of these proteins. It could be hypothesized, for example, that many of the functions initially attributed to TSP 1 could be shared by other members of the family, contingent on cell-or site-specific expression.…”

Section: Introductionmentioning

confidence: 99%

Differential expression of thrombospondin 1, 2, and 3 during murine development

Iruela‐Arispe

Liska

Sage

et al. 1993

Developmental Dynamics

210

168

View full text Add to dashboard Cite

Thrombospondin 1 is a secreted, trimeric glycoprotein that mediates interactions between cells and extracellular matrix and exhibits cell-specific effects on migration and proliferation. Recently, two additional thrombospondin genes (thrombospondin 2 and 3) have been identified. To study the functions of these proteins, we have used in situ hybridization and RNAse protection assays to compare the expression of the genes encoding thrombospondin 1, 2, and 3 during murine embryogenesis. Thrombospondin mRNAs were associated with ossification, neuronal organogenesis, and lung development, although transcripts were differentially expressed. Thrombospondin 1 was predominant from days 10 to 13. During this period, high but transient levels of expression were observed in the neural tube, head mesenchyme, and cardiac cushions. In contrast, a more constant level of thrombospondin 1 mRNA was apparent in resident megakaryocytes of the liver, as well as in circulating megakaryocytes; neither thrombospondin 2 nor 3 was detected in these cells. Thrombospondin 1 was also produced by cells of the developing kidney and gut. The expression of thrombospondin 2 was confined principally to organized connective tissue that included pericardium, pleura, perichondrium, periosteum, meninges, ligaments, and reticular dermis. Thrombospondin 2 was also produced by differentiating skeletal myoblasts and by cells of the kidney and gut. Moreover, high levels of expression were detected in blood vessels. Thrombospondin 3 mRNA was restricted to brain, cartilage, and lung. Although thrombospondin 1, 2, and 3 belong to a family of structurally related genes, the differences observed in the spatiotemporal distribution of the corresponding mRNAs indicate unique functions for these secreted proteins. 0 1993 Wiley-Liss, Inc.

show abstract

“…26 TSP-2, in contrast, does not contain unpaired cysteine. 29,30 The TSP-1 thiol is remarkably fluid and can reside on any one of 12 different cysteines in the Ca ϩϩ -binding repeats and C-terminal sequence of TSP-1 on release from platelets and chelation of Ca ϩϩ with EDTA. 26 In contrast, TSP-1 purified in buffers containing 0.1 mM Ca ϩϩ is a homogeneous TSP-1 population in that the free thiol is at Cys974.…”

Section: Discussionmentioning

confidence: 99%

“…The TSP family consists of 5 members in vertebrates, TSP-1 through TSP-4 [28][29][30][31][32] and TSP-5 (also known as cartilage oligomeric matrix protein). 33 A single member, dTSP, has also been identified in Drosophila.…”

Section: Discussionmentioning

confidence: 99%

The von Willebrand factor–reducing activity of thrombospondin-1 is located in the calcium-binding/C-terminal sequence and requires a free thiol at position 974

Pimanda

Annis²,

Raftery³

et al. 2002

Blood

View full text Add to dashboard Cite

IntroductionPlatelet adhesion to von Willebrand factor (VWF) in the subendothelium of a damaged blood vessel is the initial step in formation of a hemostatic plug at high shear rates (for a review, see Sadler 1 ). VWF also acts in synergy with fibrinogen in the formation of interplatelet adhesive links to form a stable thrombus at arterial shear rates. 2,3 As a carrier for procoagulant factor VIII, VWF prolongs its survival in the circulation by protecting it from inactivation by activated protein C and factor Xa. VWF is synthesized by vascular endothelial cells and megakaryocytes and circulates in blood as a series of multimers containing a variable number of about 500-kDa homodimers. 4 The largest VWF multimers have a molecular mass of approximately 20 000 kDa, comparable in length to the diameter of a medium platelet (2 M), and are released from endothelial cells following stimulation.The assembly of VWF multimers follows a stepwise process. Pro-VWF dimers are assembled in the endoplasmic reticulum via disulfide bridges between cysteine residues located in the cysteine knotlike domains at the C-terminal ends of the pro-VWF subunits. Intersubunit disulfide bonds involve 1 or 3 of the cysteine residues at positions 2008, 2010, and 2048. 5 These tail-to-tail linked pro-VWF dimers are subsequently multimerized within the Golgi apparatus by head-to-head linkage by disulfide bonds near the N-terminal domains. 6 Interdimeric disulfide bonds involve Cys379 and one or more of the cysteine residues at positions 459, 462, and 464. 7 After multimerization, the VWF propeptides are removed by proteolysis. 6 Only large multimeric forms of VWF are hemostatically active. 8 The unusually large VWF multimers secreted by endothelial cells have been shown to be more effective than the largest plasma forms in inducing platelet aggregation under conditions of high fluid shear. 9 This functional importance of multimer size relates to the affinity of VWF for its ligands. Large VWF multimers bind with an approximate 100-fold greater affinity to both collagen and platelets than monomeric VWF. 8 Some thrombotic disorders are characterized by altered VWF multimer size. Thrombotic thrombocytopenic purpura (TTP) is often associated with unusually large VWF multimers in the blood, which are thought to precipitate intravascular platelet clumping. 10,11 Conversely, lower than average multimer size characterizes the bleeding diathesis of type IIA von Willebrand disease. Modulation of VWF multimer size is, therefore, critical to the control of its hemostatic activity.We recently reported that the homotrimeric glycoprotein, thrombospondin-1 (TSP-1; for a review, see Lawler 12 ), reduces the average multimer size of plasma or purified VWF both in vitro and in vivo. 13,14 Incubation of TSP-1 with VWF results in formation of thiol-dependent complexes of TSP-1 and VWF, generation of new thiols in VWF, and reduction in the average multimer size of VWF. Moreover, the ratio of the concentrations of TSP-1 and VWF in plasma reflect the average multimer ...

show abstract

Thrombospondin II: Partial cDNA sequence, chromosome location, and expression of a second member of the thrombospondin gene family in humans

Cited by 46 publications

References 56 publications

Disulfide Connectivity of Recombinant C-terminal Region of Human Thrombospondin 2

Disulfide Connectivity of Recombinant C-terminal Region of Human Thrombospondin 2

Differential expression of thrombospondin 1, 2, and 3 during murine development

The von Willebrand factor–reducing activity of thrombospondin-1 is located in the calcium-binding/C-terminal sequence and requires a free thiol at position 974

Contact Info

Product

Resources

About