ErbB2, also called Neu and Her2, is a transmembrane glycoprotein in the ErbB family of tyrosine kinase receptors for EGF superfamily growth factors. ErbB2 is widely expressed in epithelial cells and over-expressed in a large number of breast carcinomas. ErbB2 has no identified ligands but heterodimerizes with ErbB1/EGF R, ErbB3, or ErbB4 to form higher affinity signaling complexes. The protease ADAM10 releases a 110 kDa soluble fragment of ErbB2 from the cell surface. ErbB2 plays roles in development, cancer, communication at the neuromuscular junction, and regulation of cell growth and differentiation. The ErbB2/ErbB3 heterodimer is expressed in the majority of breast, skin, ovary and gastrointestinal tumors and transduces a highly mitogenic signal in response to neuregulin 1 (NRG1; heuregulin 1) or NRG2. ErbB3, ErbB2 and neuregulin are all required for formation of the sympathetic nervous system.
This gene encodes a member of the epidermal growth factor (EGF) receptor family of receptor tyrosine kinases. This protein has no ligand binding domain of its own and therefore cannot bind growth factors. However, it does bind tightly to other ligand-bound EGF receptor family members to form a heterodimer, stabilizing ligand binding and enhancing kinase-mediated activation of downstream signalling pathways, such as those involving mitogen-activated protein kinase and phosphatidylinositol-3 kinase. Allelic variations at amino acid positions 654 and 655 of isoform a (positions 624 and 625 of isoform b) have been reported, with the most common allele, Ile654/Ile655, shown here. Amplification and/or overexpression of this gene has been reported in numerous cancers, including breast and ovarian tumors.
HER4/ErbB4, like other receptor tyrosine kinase family members, has four ectodomains, a single transmembrane domain and a cytoplasmic tail containing the active tyrosine kinase domain. By binding to neuregulins and/or EGF family ligands, ErbB4 forms either a homodimer or heterodimer with other ErbB family members, which results in receptor activation and signaling. ErbB4 is ubiquitously expressed with the highest expression occurring in brain and heart. The expression of ErbB4 in breast cancer, pediatric brain cancer and other types of carcinomas has been reported in research studies suggesting that ErbB4 expression is involved in both normal tissue development and carcinogenesis.
This protein belongs to the basic helix-loop-helix family of transcription factors. It is a transcriptional repressor of genes that require a bHLH protein for their transcription. The protein has a particular type of basic domain that contains a helix interrupting protein that binds to the N-box rather than the canonical E-box.
HES5, also known as bHLHb38, has a particular type of basic domain (presence of a helix-interrupting proline) that binds to the N-box (CACNAG), rather than the canonical E-box (CANNTG). HES5 is expressed in fetal heart and brain tumors. HES5 as a transcriptional repressor of genes that require a bHLH protein for their transcription and plays an important role as neurogenesis negative regulator.
Hexokinases phosphorylate glucose to produce glucose-6-phosphate, the first step in most glucose metabolism pathways. This gene encodes hexokinase 2, the predominant form found in skeletal muscle. It localizes to the outer membrane of mitochondria. Expression of this gene is insulin-responsive, and studies in rat suggest that it is involved in the increased rate of glycolysis seen in rapidly growing cancer cells.
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