Thrombospondin-2 Explained

Thrombospondin-2 is a protein that in humans is encoded by the THBS2 gene.^{[1] [2]}

The protein encoded by this gene belongs to the thrombospondin family. It is a disulfide-linked homotrimeric glycoprotein that mediates cell-to-cell and cell-to-matrix interactions. The role of the protein in cancer is controversial, contrasting studies show positive and negative roles for cancer development. Studies of the mouse counterpart suggest that this protein may modulate the cell surface properties of mesenchymal cells and be involved in cell adhesion and migration.^[2]

Interactions

THBS2 has been shown to interact with MMP2.^[3]

Further reading

• Bornstein P, Kyriakides TR, Yang Z, Armstrong LC, Birk DE . Thrombospondin 2 modulates collagen fibrillogenesis and angiogenesis . The Journal of Investigative Dermatology. Symposium Proceedings . 5 . 1 . 61–6 . Dec 2000 . 11147677 . 10.1046/j.1087-0024.2000.00005.x . free .
• O'Rourke KM, Laherty CD, Dixit VM . Thrombospondin 1 and thrombospondin 2 are expressed as both homo- and heterotrimers . The Journal of Biological Chemistry . 267 . 35 . 24921–4 . Dec 1992 . 10.1016/S0021-9258(19)73983-0 . 1459996 . free .
• LaBell TL, Milewicz DJ, Disteche CM, Byers PH . Thrombospondin II: partial cDNA sequence, chromosome location, and expression of a second member of the thrombospondin gene family in humans . Genomics . 12 . 3 . 421–9 . Mar 1992 . 1559694 . 10.1016/0888-7543(92)90430-Z .
• LaBell TL, Byers PH . Sequence and characterization of the complete human thrombospondin 2 cDNA: potential regulatory role for the 3' untranslated region . Genomics . 17 . 1 . 225–9 . Jul 1993 . 8406456 . 10.1006/geno.1993.1308 .
• Adolph KW, Liska DJ, Bornstein P . Analysis of the promoter and transcription start sites of the human thrombospondin 2 gene (THBS2) . Gene . 193 . 1 . 5–11 . Jul 1997 . 9249061 . 10.1016/S0378-1119(97)00070-X .
• Kyriakides TR, Zhu YH, Smith LT, Bain SD, Yang Z, Lin MT, Danielson KG, Iozzo RV, LaMarca M, McKinney CE, Ginns EI, Bornstein P . Mice that lack thrombospondin 2 display connective tissue abnormalities that are associated with disordered collagen fibrillogenesis, an increased vascular density, and a bleeding diathesis . The Journal of Cell Biology . 140 . 2 . 419–30 . Jan 1998 . 9442117 . 2132586 . 10.1083/jcb.140.2.419 .
• Adolph KW . Relative abundance of thrombospondin 2 and thrombospondin 3 mRNAs in human tissues . Biochemical and Biophysical Research Communications . 258 . 3 . 792–6 . May 1999 . 10329465 . 10.1006/bbrc.1999.0710 .
• Carron JA, Bowler WB, Wagstaff SC, Gallagher JA . Expression of members of the thrombospondin family by human skeletal tissues and cultured cells . Biochemical and Biophysical Research Communications . 263 . 2 . 389–91 . Sep 1999 . 10491303 . 10.1006/bbrc.1999.1380 .
• Bein K, Simons M . Thrombospondin type 1 repeats interact with matrix metalloproteinase 2. Regulation of metalloproteinase activity . The Journal of Biological Chemistry . 275 . 41 . 32167–73 . Oct 2000 . 10900205 . 10.1074/jbc.M003834200 . free .
• Hawighorst T, Velasco P, Streit M, Hong YK, Kyriakides TR, Brown LF, Bornstein P, Detmar M . Thrombospondin-2 plays a protective role in multistep carcinogenesis: a novel host anti-tumor defense mechanism . The EMBO Journal . 20 . 11 . 2631–40 . Jun 2001 . 11387198 . 125494 . 10.1093/emboj/20.11.2631 .
• Misenheimer TM, Hahr AJ, Harms AC, Annis DS, Mosher DF . Disulfide connectivity of recombinant C-terminal region of human thrombospondin 2 . The Journal of Biological Chemistry . 276 . 49 . 45882–7 . Dec 2001 . 11590138 . 10.1074/jbc.M104218200 . free .
• Armstrong DJ, Hiscott P, Batterbury M, Kaye S . Corneal stromal cells (keratocytes) express thrombospondins 2 and 3 in wound repair phenotype . The International Journal of Biochemistry & Cell Biology . 34 . 6 . 588–93 . Jun 2002 . 11943589 . 10.1016/S1357-2725(01)00157-1 .
• Li Z, Calzada MJ, Sipes JM, Cashel JA, Krutzsch HC, Annis DS, Mosher DF, Roberts DD . Interactions of thrombospondins with alpha4beta1 integrin and CD47 differentially modulate T cell behavior . The Journal of Cell Biology . 157 . 3 . 509–19 . Apr 2002 . 11980922 . 2173289 . 10.1083/jcb.200109098 .
• Armstrong LC, Björkblom B, Hankenson KD, Siadak AW, Stiles CE, Bornstein P . Thrombospondin 2 inhibits microvascular endothelial cell proliferation by a caspase-independent mechanism . Molecular Biology of the Cell . 13 . 6 . 1893–905 . Jun 2002 . 12058057 . 117612 . 10.1091/mbc.E01-09-0066 .
• Hatakeyama H, Nishizawa M, Nakagawa A, Nakano S, Kigoshi T, Miyamori I, Uchida K . Thrombospondin expression in aldosterone-producing adenomas . Hypertension Research . 25 . 4 . 523–7 . Jul 2002 . 12358136 . 10.1291/hypres.25.523 . free .
• Boekholdt SM, Trip MD, Peters RJ, Engelen M, Boer JM, Feskens EJ, Zwinderman AH, Kastelein JJ, Reitsma PH . Thrombospondin-2 polymorphism is associated with a reduced risk of premature myocardial infarction . Arteriosclerosis, Thrombosis, and Vascular Biology . 22 . 12 . e24–7 . Dec 2002 . 12482844 . 10.1161/01.ATV.0000046235.22451.66 . free .
• Kyriakides TR, Rojnuckarin P, Reidy MA, Hankenson KD, Papayannopoulou T, Kaushansky K, Bornstein P . Megakaryocytes require thrombospondin-2 for normal platelet formation and function . Blood . 101 . 10 . 3915–23 . May 2003 . 12732502 . 10.1182/blood.V101.10.3915 . free .
• Kishi M, Nakamura M, Nishimine M, Ishida E, Shimada K, Kirita T, Konishi N . Loss of heterozygosity on chromosome 6q correlates with decreased thrombospondin-2 expression in human salivary gland carcinomas . Cancer Science . 94 . 6 . 530–5 . Jun 2003 . 12824879 . 10.1111/j.1349-7006.2003.tb01478.x . 19472764 . free . 11160221 .

Notes and References

1. Hirose Y, Chiba K, Karasugi T, Nakajima M, Kawaguchi Y, Mikami Y, Furuichi T, Mio F, Miyake A, Miyamoto T, Ozaki K, Takahashi A, Mizuta H, Kubo T, Kimura T, Tanaka T, Toyama Y, Ikegawa S . A functional polymorphism in THBS2 that affects alternative splicing and MMP binding is associated with lumbar-disc herniation . American Journal of Human Genetics . 82 . 5 . 1122–9 . May 2008 . 18455130 . 2427305 . 10.1016/j.ajhg.2008.03.013 .
2. Web site: Entrez Gene: THBS2 thrombospondin 2.
3. Bein K, Simons M . Thrombospondin type 1 repeats interact with matrix metalloproteinase 2. Regulation of metalloproteinase activity . The Journal of Biological Chemistry . 275 . 41 . 32167–73 . Oct 2000 . 10900205 . 10.1074/jbc.M003834200 . free .