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Thrombospondin-1

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Encyclopedia of Signaling Molecules

Synonyms

Glycoprotein G; THBS1; Thrombospondin; TSP1

Historical Background

Thrombospondin-1 (TSP1) was first characterized in 1971 by Baenziger et al. as a glycoprotein released from the α-granules of platelets in response to treatment with thrombin (Roberts and Lau 2011). This large protein consists of three 150 kDa disulfide-linked subunits and is highly conserved among vertebrate species (Carlson et al. 2008). Multi-sequence analysis has generated a phylogenetic tree for the evolution of modern TSPs (Bentley and Adams 2010). Duplication of the gene encoding a primordial TSP that is currently found in insects initiated the evolution of two subfamilies containing five members in modern vertebrates (Bentley and Adams 2010). The central feature of all TSPs is the presence of a carboxy-terminal signature domain containing EGF-like modules and seven TSP-type Ca-binding repeats, which wrap around the C-terminal lectin-like globular domain. This domain is about 650 amino acids long and is...

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References

  • Bentley AA, Adams JC. The evolution of thrombospondins and their ligand-binding activities. Mol Biol Evol. 2010;27:2187–97.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bornstein P, Alfi D, Devarayalu S, Framson P, Li P. Characterization of the mouse thrombospondin gene and evaluation of the role of the first intron in human gene expression. J Biol Chem. 1990;265:16691–8.

    PubMed  CAS  Google Scholar 

  • Carlson CB, Lawler J, Mosher DF. Structures of thrombospondins. Cell Mol Life Sci. 2008;65:672–86.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Isenberg JS, Martin-Manso G, Maxhimer JB, Roberts DD. Regulation of nitric oxide signaling by thrombospondin 1: implications for anti-angiogenic therapies. Nat Rev Cancer. 2009;9:182–94.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kaur S, Roberts DD. Divergent modulation of normal and neoplastic stem cells by thrombospondin-1 and CD47 signaling. Int J Biochem Cell Biol. 2016; 81:184–194. https://doi.org/10.1016/j.biocel.2016.05.005.

    Article  CAS  Google Scholar 

  • Kaur S, Martin-Manso G, Pendrak ML, Garfield SH, Isenberg JS, Roberts DD. Thrombospondin-1 inhibits VEGF receptor-2 signaling by disrupting its association with CD47. J Biol Chem. 2010;285:38923–32.

    Article  CAS  Google Scholar 

  • Kazerounian S, Duquette M, Reyes MA, Lawler JT, Song K, Perruzzi C, et al. Priming of the vascular endothelial growth factor signaling pathway by thrombospondin-1, CD36, and spleen tyrosine kinase. Blood. 2011;117:4658–66.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Labrousse-Arias D, Castillo-González R, Rogers NM, Torres-Capelli M, Barreira B, Aragonés J, Cogolludo Á, Isenberg JS, Calzada MJ. HIF-2α-mediated induction of pulmonary thrombospondin-1 contributes to hypoxia-driven vascular remodelling and vasoconstriction. Cardiovasc Res. 2016;109:115–30.

    Article  PubMed  CAS  Google Scholar 

  • Lopez-Dee Z, Pidcock K, Gutierrez LS. Thrombospondin-1: multiple paths to inflammation. Mediators Inflamm. 2011;2011:296069.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lu A, Pallero MA, Lei W, Hong H, Yang Y, Suto MJ, Murphy-Ullrich JE. Inhibition of transforming growth factor-β activation diminishes tumor progression and osteolytic bone disease in mouse models of multiple myeloma. Am J Pathol. 2016;186:678–90.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Markovic SN, Suman VJ, Rao RA, Ingle JN, Kaur JS, Erickson LA, et al. A phase II study of ABT-510 (thrombospondin-1 analog) for the treatment of metastatic melanoma. Am J Clin Oncol. 2007;30:303–9.

    Article  PubMed  CAS  Google Scholar 

  • Maxhimer JB, Soto-Pantoja DR, Ridnour LA, Shih HB, Degraff WG, Tsokos M, et al. Radioprotection in normal tissue and delayed tumor growth by blockade of CD47 signaling. Sci Transl Med. 2009;1:3ra7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Miller TW, Soto-Pantoja DR, Schwartz AL, Sipes JM, DeGraff WG, Ridnour LA, Wink DA, Roberts DD. CD47 globally regulates metabolic pathways that control resistance to ionizing radiation. J Biol Chem. 2015;290:24858–74.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Roberts DD, Lau L. Matricellular proteins. In: Mecham RP, editor. Biology of extracellular matrix: an overview. Berlin/Heidelberg: Springer; 2011. p. 369–413.

    Chapter  Google Scholar 

  • Rogers NM, Yao M, Novelli EM, Thomson AW, Roberts DD, Isenberg JS. Activated CD47 regulates multiple vascular and stress responses: implications for acute kidney injury and its management. Am J Physiol Renal Physiol. 2012;303:F1117–25. https://doi.org/10.1152/ajprenal.00359.2012.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Soto-Pantoja DR, Kaur S, Roberts DD. CD47 signaling pathways controlling cellular differentiation and responses to stress. Crit Rev Biochem Mol Biol. 2015;24:1–19.

    Google Scholar 

  • Soto-Pantoja DR, Sipes JM, Martin-Manso G, Westwood B, Morris NL, Ghosh A, Emenaker NJ, Roberts DD. Dietary fat overcomes the protective activity of thrombospondin-1 signaling in the Apc(Min/+) model of colon cancer. Oncogenesis. 2016;5:e230.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Stein EV, Miller TW, Ivins-O’Keefe K, Kaur S, Roberts DD. Secreted thrombospondin-1 regulates macrophage interleukin-1β production and activation through CD47. Sci Rep. 2016;27:19684.

    Article  CAS  Google Scholar 

  • Takahashi K, Sumarriva K, Kim R, Jiang R, Brantley-Sieders DM, Chen J, Mernaugh RL, Takahashi T. Determination of the CD148-interacting region in thrombospondin-1. PLoS One. 2016;11:e0154916.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Visavadiya NP, Li Y, Wang S. High glucose upregulates upstream stimulatory factor 2 in human renal proximal tubular cells through angiotensin II-dependent activation of CREB. Nephron Exp Nephrol. 2011;117:e62–70.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to David R. Soto-Pantoja .

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Roberts, D.D., Kaur, S., Soto-Pantoja, D.R. (2018). Thrombospondin-1. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_637

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