Encyclopedia of Signaling Molecules

2012 Edition
| Editors: Sangdun Choi

Thrombospondin-1

Reference work entry
DOI: https://doi.org/10.1007/978-1-4419-0461-4_637

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...
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References

  1. Bauer EM, Qin Y, Miller TW, Bandle RW, Csanyi G, Pagano PJ, et al. Thrombospondin-1 supports blood pressure by limiting eNOS activation and endothelial-dependent vasorelaxation. Cardiovasc Res. 2010;88:471–81.PubMedGoogle Scholar
  2. Bentley AA, Adams JC. The evolution of thrombospondins and their ligand-binding activities. Mol Biol Evol. 2010;27:2187–97.PubMedGoogle Scholar
  3. 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
  4. Carlson CB, Lawler J, Mosher DF. Structures of thrombospondins. Cell Mol Life Sci. 2008;65:672–86.PubMedGoogle Scholar
  5. Frazier WA, Isenberg JS, Kaur S, Roberts DD. CD47. Nature signaling gateway. 2010. Available from: http://www.signaling-gateway.org/molecule/query?afcsid=A002870. Accessed 16 Feb 2010.
  6. Frazier EP, Isenberg JS, Shiva S, Zhao L, Schlesinger P, Dimitry J, et al. Age-dependent regulation of skeletal muscle mitochondria by the thrombospondin-1 receptor CD47. Matrix Biol. 2011;30:154–61.PubMedGoogle Scholar
  7. Isenberg JS, Frazier WA, Krishna MC, Wink DA, Roberts DD. Enhancing cardiovascular dynamics by inhibition of thrombospondin-1/CD47 signaling. Curr Drug Targets. 2008;9:833–41.PubMedGoogle Scholar
  8. Isenberg JS, Martin-Manso G, Maxhimer JB, Roberts DD. Regulation of nitric oxide signalling by thrombospondin 1: implications for anti-angiogenic therapies. Nat Rev Cancer. 2009;9:182–94.PubMedGoogle Scholar
  9. 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.PubMedGoogle Scholar
  10. Kaur S, Kuznetsova SA, Pendrak ML, Sipes JM, Romeo MJ, Li Z, et al. Heparan sulfate modification of the transmembrane receptor CD47 is necessary for inhibition of T cell receptor signaling by thrombospondin-1. J Biol Chem. 2011;286:14991–5002.PubMedGoogle Scholar
  11. 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.PubMedGoogle Scholar
  12. Lopez-Dee Z, Pidcock K, Gutierrez LS. Thrombospondin-1: multiple paths to inflammation. Mediators Inflamm. 2011;2011:296069.PubMedGoogle Scholar
  13. 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.PubMedGoogle Scholar
  14. 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.PubMedGoogle Scholar
  15. Miller TW, Isenberg JS, Roberts DD. Thrombospondin-1 is an inhibitor of pharmacological activation of soluble guanylate cyclase. Br J Pharmacol. 2010;159:1542–7.PubMedGoogle Scholar
  16. Nabors LB, Fiveash JB, Markert JM, Kekan MS, Gillespie GY, Huang Z, et al. A phase 1 trial of ABT-510 concurrent with standard chemoradiation for patients with newly diagnosed glioblastoma. Arch Neurol. 2010;67:313–9.PubMedGoogle Scholar
  17. Roberts DD, Lau L. Matricellular proteins. In: Mecham RP, editor. Biology of extracellular matrix: an overview. Berlin/Heidelberg: Springer; 2011. p. 369–413.Google Scholar
  18. Su F, Pascal LE, Xiao W, Wang Z. Tumor suppressor U19/EAF2 regulates thrombospondin-1 expression via p53. Oncogene. 2010;29:421–31.PubMedGoogle Scholar
  19. 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.PubMedGoogle Scholar
  20. Yao M, Roberts DD, Isenberg JS. Thrombospondin-1 inhibition of vascular smooth muscle cell responses occurs via modulation of both cAMP and cGMP. Pharmacol Res. 2011;63:13–22.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Laboratory of PathologyCenter for Cancer Research, National Cancer Institute, National Institutes of HealthBethesdaUSA