Betacellulin

Betacellulin is a protein that in humans is encoded by the BTC gene located on chromosome 4 at locus 4q13-q21. Betacellulin is a member of the EGF family of growth factors. It is synthesized primarily as a transmembrane precursor, which is then processed to mature molecule by proteolytic events. This protein is a ligand for the EGF receptor.

Structure

BTC is a polymer of about 62-111 amino acid residues. Secondary Structure: 6% helical (1 helices; 3 residues) 36% beta sheet (5 strands; 18 residues)

• BTC was originally identified as a growth-promoting factor in mouse pancreatic β-cell carcinoma cell line and has since been identified in humans. Mouse BTC (mBTC) is expressed as a 178-amino acid precursor. The membrane-bound precursor is cleaved to yield mature secreted mBTC. BTC is synthesized in a wide range of adult tissues and in many cultured cells, including smooth muscle cells and epithelial cells. The amino acid sequence of mature mBTC is 82.5%, identical with that of human BTC (hBTC), and both exhibit significant overall similarity with other members of the EGF family.

About the Image

• The structure for the small protein Betacellulin that is shown was determined by two-dimensional nuclear magnetic resonance spectroscopy. The species that BTC was taken from was Homo sapiens.This particular molecule of BTC has a formula weight of 5916.9 and its sequence was determined to be RKGHFSRCPKQYKHYCIKGRCRFVVAEQTPSCVCDEGYIGARCERVDLFY (if you would like to see an image of what parts of the sequence code for the secondary structures observed in the image, click here). Also, a Ramachandran plot can be found here.

Further reading

• Kim HS, Shin HS, Kwak HJ, Cho CH, Lee CO, Koh GY (February 2003). "Betacellulin induces angiogenesis through activation of mitogen-activated protein kinase and phosphatidylinositol 3'-kinase in endothelial cell". FASEB J. 17 (2): 318–20. doi:10.1096/fj.02-0570fje. PMID 12475887.
• Yamamoto T, Akisue T, Marui T, et al. (2004). "Expression of betacellulin, heparin-binding epidermal growth factor and epiregulin in human malignant fibrous histiocytoma". Anticancer Res. 24 (3b): 2007–10. PMID 15274392.
• Nakagawa T, Furuta H, Sanke T, et al. (2005). "Molecular scanning of the betacellulin gene for mutations in type 2 diabetic patients". Diabetes Res. Clin. Pract. 68 (3): 188–92. doi:10.1016/j.diabres.2004.09.019. PMID 15936459.
• Silver K, Tolea M, Wang J, et al. (2005). "The exon 1 Cys7Gly polymorphism within the betacellulin gene is associated with type 2 diabetes in African Americans". Diabetes. 54 (4): 1179–84. doi:10.2337/diabetes.54.4.1179. PMID 15793259.
• Tanimura K, Nakago S, Murakoshi H, et al. (2004). "Changes in the expression and cytological localization of betacellulin and its receptors (ErbB-1 and ErbB-4) in the trophoblasts in human placenta over the course of pregnancy". Eur. J. Endocrinol. 151 (1): 93–101. doi:10.1530/eje.0.1510093. PMID 15248827.
• Saito T, Okada S, Ohshima K, et al. (2004). "Differential activation of epidermal growth factor (EGF) receptor downstream signaling pathways by betacellulin and EGF". Endocrinology. 145 (9): 4232–43. doi:10.1210/en.2004-0401. PMID 15192046.
• Elbein SC, Wang X, Karim MA, et al. (2006). "Analysis of coding variants in the betacellulin gene in type 2 diabetes and insulin secretion in African American subjects". BMC Med. Genet. 7: 62. doi:10.1186/1471-2350-7-62. PMC 1544326. PMID 16869959.
• Genetos DC, Rao RR, Vidal MA (2010). "Betacellulin inhibits osteogenic differentiation and stimulates proliferation through HIF-1alpha". Cell Tissue Res. 340 (1): 81–9. doi:10.1007/s00441-010-0929-0. PMC 2847694. PMID 20165885.
• Moss ML, Bomar M, Liu Q, et al. (2007). "The ADAM10 prodomain is a specific inhibitor of ADAM10 proteolytic activity and inhibits cellular shedding events". J. Biol. Chem. 282 (49): 35712–21. doi:10.1074/jbc.M703231200. PMID 17895248.
• Rittié L, Kansra S, Stoll SW, et al. (2007). "Differential ErbB1 signaling in squamous cell versus basal cell carcinoma of the skin". Am. J. Pathol. 170 (6): 2089–99. doi:10.2353/ajpath.2007.060537. PMC 1899432. PMID 17525275.
• Révillion F, Lhotellier V, Hornez L, et al. (2008). "ErbB/HER ligands in human breast cancer, and relationships with their receptors, the bio-pathological features and prognosis". Ann. Oncol. 19 (1): 73–80. doi:10.1093/annonc/mdm431. PMID 17962208.
• Silver KD, Shi X, Mitchell BD (2007). "Betacellulin variants and type 2 diabetes in the Old Order Amish". Exp. Clin. Endocrinol. Diabetes. 115 (4): 229–31. doi:10.1055/s-2007-970575. PMID 17479438.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Mehrle A, Rosenfelder H, Schupp I, et al. (2006). "The LIFEdb database in 2006". Nucleic Acids Res. 34 (Database issue): D415–8. doi:10.1093/nar/gkj139. PMC 1347501. PMID 16381901.
• Stoeck A, Shang L, Dempsey PJ (2010). "Sequential and gamma-secretase-dependent processing of the betacellulin precursor generates a palmitoylated intracellular-domain fragment that inhibits cell growth". J. Cell Sci. 123 (Pt 13): 2319–31. doi:10.1242/jcs.060830. PMC 2886747. PMID 20530572.
• Nagaoka T, Fukuda T, Hashizume T, et al. (2008). "A betacellulin mutant promotes differentiation of pancreatic acinar AR42J cells into insulin-producing cells with low affinity of binding to ErbB1". J. Mol. Biol. 380 (1): 83–94. doi:10.1016/j.jmb.2008.03.054. PMID 18508082.
• Nakano Y, Furuta H, Doi A, et al. (2005). "A functional variant in the human betacellulin gene promoter is associated with type 2 diabetes". Diabetes. 54 (12): 3560–6. doi:10.2337/diabetes.54.12.3560. PMID 16306376.
• Sanderson MP, Erickson SN, Gough PJ, et al. (2005). "ADAM10 mediates ectodomain shedding of the betacellulin precursor activated by p-aminophenylmercuric acetate and extracellular calcium influx". J. Biol. Chem. 280 (3): 1826–37. doi:10.1074/jbc.M408804200. PMID 15507448.
• Dunbar AJ, Goddard C (2000). "Structure-function and biological role of betacellulin". Int. J. Biochem. Cell Biol. 32 (8): 805–15. doi:10.1016/S1357-2725(00)00028-5. PMID 10940639.
• Wiemann S, Arlt D, Huber W, et al. (2004). "From ORFeome to biology: a functional genomics pipeline". Genome Res. 14 (10B): 2136–44. doi:10.1101/gr.2576704. PMC 528930. PMID 15489336.
• Silver KD, Magnuson VL, Tolea M, et al. (2006). "Association of a polymorphism in the betacellulin gene with type 1 diabetes mellitus in two populations". J. Mol. Med. 84 (7): 616–23. doi:10.1007/s00109-006-0052-6. PMID 16683131.

External links

• Betacellulin at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.