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 part of an Epidermal Growth Factor (EGF) family and functions as a ligand for the epidermal growth factor receptor (EGFR). As the role a EGFR, betacellulin is manifested by different form of muscles and tissues, it also has a great effect of nitrogen that is used for retinal pigment epithelial cells and vascular smooth muscle cells. While many studies attest a role for betacellulin in the differentiation of pancreatic β-cells, the last decade witnessed the association of betacellulin with many additional biological processes, ranging from reproduction to the control of neural stem cells. 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. 
As a typical EGFR ligand, betacellulin is expressed by a variety of cell types and tissues, and the soluble growth factor is proteolytically cleaved from a larger membrane-anchored precursor. Betacellulin stimulates the proliferation of retinal pigment epithelial and vascular smooth muscle cells but did not stimulate the growth of several other cell types, such as endothelial cells and fetal lung fibroblasts. Osteoblasts, which are responsible for forming and mineralizing osteoid, express EGF receptors and alter rates of proliferation and differentiation in response to EGF receptor activation. Transgenic mice over-expressing the EGF-like ligand betacellulin (BTC) exhibit increased cortical bone deposition; however, because the transgene is ubiquitously expressed in these mice, the identity of cells affected by BTC and responsible for increased cortical bone thickness remains unknown. BTC decreases the expression of osteogenic markers in both MSCs and pre-osteoblasts increases in proliferation require hypoxia-inducible factor-alpha (HIF-alpha), as an HIF antagonist prevents BTC-driven proliferation. Both MSCs and pre-osteoblasts express EGF receptors ErbB1, ErbB2, and ErbB3, with no change in expression under osteogenic differentiation. These are the first data that demonstrate an influence of BTC upon MSCs and the first to implicate HIF-alpha in BTC-mediated proliferation. The mRNA coding for betacellulin was found to be slightly higher compared in the rat sciatic nerve segment after nerve damage, suggesting that betacellulin can play a role in peripheral nerve regeneration. Immunohistochemistry has been used to look for betacellulin expression in Schwann cells. Treating cells with betacellulin recombinant protein can be used to investigate the role of betacellulin in managing Schwann cells. A co-culture assay can also used to assess the effect of Schwann cell-secreted betacellulin on neurons. 
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)
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.