Encyclopedia of Signaling Molecules

Living Edition
| Editors: Sangdun Choi

Thrombospondin-1

  • David D. Roberts
  • Sukhbir Kaur
  • David R. Soto-Pantoja
Living reference work entry
DOI: https://doi.org/10.1007/978-1-4614-6438-9_637-1

Synonyms

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...

Keywords

Obesity Migration Recombination Superoxide Heparin 
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References

  1. Bentley AA, Adams JC. The evolution of thrombospondins and their ligand-binding activities. Mol Biol Evol. 2010;27:2187–97.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 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.PubMedGoogle Scholar
  3. Carlson CB, Lawler J, Mosher DF. Structures of thrombospondins. Cell Mol Life Sci. 2008;65:672–86.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 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. doi: 10.1016/j.biocel.2016.05.005.
  6. 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.Google Scholar
  7. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 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.CrossRefPubMedGoogle Scholar
  9. Lopez-Dee Z, Pidcock K, Gutierrez LS. Thrombospondin-1: multiple paths to inflammation. Mediators Inflamm. 2011;2011:296069.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 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.CrossRefPubMedGoogle Scholar
  12. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  14. Roberts DD, Lau L. Matricellular proteins. In: Mecham RP, editor. Biology of extracellular matrix: an overview. Berlin/Heidelberg: Springer; 2011. p. 369–413.CrossRefGoogle Scholar
  15. 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. doi: 10.1152/ajprenal.00359.2012.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 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
  17. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 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.CrossRefGoogle Scholar
  19. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 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.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media LLC (outside the USA) 2016

Authors and Affiliations

  • David D. Roberts
    • 1
  • Sukhbir Kaur
    • 1
  • David R. Soto-Pantoja
    • 2
  1. 1.Laboratory of PathologyCenter for Cancer Research, National Cancer Institute, National Institutes of HealthBethesdaUSA
  2. 2.Departments of Surgery, Radiation Oncology & Cancer BiologyComprehensive Cancer Center, Wake Forest School of MedicineWinston-SalemUSA