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Definition
Thrombospondins comprise a family of multidomain, secreted glycoproteins that regulate cell adhesion, migration, inflammation, and platelet aggregation. The COOH-terminal cell binding domains (CBD) of thrombospondins share a higher degree of homology than other domains of thrombospondin family members. 1.

Related Peptides
Homologs of the thrombospondin-1 (TS-1) peptides are found in tenascin, a matrix protein that shares several properties with TS1 and in factor VIII, alpha 2-macroglobulin, and von Willebrand factor 2.

Discovery
This glycoprotein was first described in 1971 by Baenziger et al., and isolated in 1978 by researchers studying the mechanisms and regulation of the blood clotting process. It earned its name because it was released by platelets in response to treatment with thrombin. The protein was found to be an endogenous platelet participant in the haemagglutination process through its interactions with platelet bound fibrinogen. A multivalent molecule, it was found to have binding sites for many different molecules including collagen, fibronectin, fibrinogen, plasminogen, and calcium. Thrombospondin was also shown to be produced by other cell types including endothelial cells. Thrombospondin was thus understood early on to have an important role in the interactions of cells with other cells and with extracellular matrix. Immunostaining showed that thrombospondin was present in the interstices around multiple tissues in the body 3.

Structural Characteristics
TS1 contains at least four domains that support cell attachment. The COOH-terminal CBD was first identified with a monoclonal antibody against TS1 that blocked secretion-dependent platelet aggregation. The carboxyl-terminal CBD of TS1 contains two cell attachment peptides, 4N1s (RFYVVMWK) and 7N3 (FIRVVMY-EGKK), which share the sequence VVM 4. The octapeptide, RFYVVMWK (4N1-1), from C4 and a pentapeptide, IRVVM (7N3-1), from C7 were found to support attachment of G361 melanomas, K562 erythroleukemia cells, HT1080 fibrosarcomas, C32 amelanotic melanomas, and endothelial cells. These peptides also inhibit the adhesion of cells to the recombinant CBD of TS1. The hexapeptide RFYVVM (4N1-2) also inhibits cell attachment. The inhibitory effect of combinations of C4- and C7-derived peptides is synergistic. The sequences 4N1-1 and 7N3-1 of TS1 share homology with two cell adhesive peptides from laminin (LM), LMF9 and LMPA22-2, respectively. These TS1 and LM peptides are interchangeable in inhibiting the adhesion of G361 cells to LM or TS1, suggesting a possible sharing of receptors by LM and TS1. K562 cells, however, bind only to TS1, and this binding was inhibited preferentially by the TS1 CBD peptides, indicating a receptor specific for TS1 which does not recognize LM. The active TS1 peptides are highly conserved among five species and four isoforms of TS1 2.

Mode of Action
Integrin-associated protein (IAP; or CD47) is a receptor for the CBD of TS1. In platelets, IAP associates with and regulates the function of aIIbß3 integrin. IAP is a member of the IgG superfamily of receptors with a single IgGv extracellular domain, five transmembrane segments, and a short COOH-terminal cytoplasmic tail. IAP is involved in host defense and transendothelial migration of neutrophils (PMNs) 1.

Functions
Thrombospondins comprise a family of multidomain, secreted glycoproteins that regulate cell adhesion, migration, inflammation, and platelet aggregation 1.

References

1.     Chung J, Wang XQ, Lindberg FP, Frazier WA (1999). Thrombospondin-1 acts via iap/cd47 to synergize with collagen in ?2?1-mediated platelet activation. Blood, 94(2):642-648.

2.     Kosfeld MD, Frazier WA (1993). Identification of a new cell adhesion motif in two homologous peptides from the COOH-terminal cell binding domain of human thrombospondin. The Journal of Biological Chemistry, 268:8808-8814.

3.     Stewart JM (2006). Thrombospondin in the eye. Br J Ophthalmol., 90(1):5-6.

4. Gao AG, Frazier WA (1994). Identification of a receptor candidate for the carboxyl-terminal cell binding domain of thrombospondins. The Journal of Biological Chemistry, 269(47):29650-29657.

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Product Name Catalog # Unit Price/Unit 
Biotin Tryptophan Motif
Biotin-LC-GGWSHW-CONH2
13542-01 1 mg $245 cart inquire
KQFK
KQFK
13544-01 1 mg $200 cart inquire
LSKL, Inhibitor of Thrombospondin (TSP - 1)
LSKL-CONH2
13547-01 1 mg $120 cart inquire
SLLK, Control Peptide for TSP1 Inhibitor
SLLK-CONH2
13545-01 1 mg $120 cart inquire
TGFß activating peptide
KRFK-CONH2
13546-01 1 mg $200 cart inquire
Transforming Growth Factor ß1 Peptide, TGF - ß1 (6
KVLALYNK-CONH2
13541-01 1 mg $200 cart inquire
Tryptophan Motif Peptide
GGWSHW-CONH2
13543-01 1 mg $200 cart inquire
VLAL
VLAL-CONH2
13548-01 1 mg $200 cart inquire

Biosynthesis Inc.