The tyrosine kinase receptor erbB2, also known in humans as Her2, is a member of the epidermal growth factor receptor (EGFR or erbB1) family, which also includes erbB3 and erbB4 that are gene products of proto-oncogenes. Protocogenes play an important role in normal proliferation of cells. The interaction of proto-oncogenes with other tumor suppressor proteins (P53, P14ARF etc.) determine the normal or abnormal course of cell cycle and cell division leading to uncontrolled cell proliferation (1). Her 2 is found on chromosome 17 and codes for a protein that serves as a cell surface receptor. Her protein family of receptor has 4 structurally similar members of membrane receptors that have intrinsic tyrosine kinase activity. These Her receptors working in concert, determine the regulation of cell growth and differentiation in a complex manner. Her-2 receptor is still considered to be an orphan receptor with no identifiable ligand. Her family receptors can form homo or hetero dimers with other compounds. The activation of these homo-heterodimmeric complexes by ligand binding led to an activation of intrinsic tyrosine kinase activity that triggers a cascade of signal transduction activity in cell. Some of these signals are transduced across the cell membranes in to cytoplasm and triggers the gene activation. A better understanding of these receptors and identification of their respective ligands will greatly enhance our understanding of cell cycle and uncontrolled cell division as seen in cancerous tissues. Several steps in these pathways are currently being targeted for therapeutic intervention, including tyrosine kinase inhibitors. There are at least 2 humanized recombinant monoclonal antibodies (Trastuzumab and pertuzumab) that target extra cellular regions of the Her 2 tyrosine kinase receptor and have been used in human trials for the treatment of breast cancer (2).
Herceptin-2 is a 1342 amino acid protein (approximate MW 170-172 kDa) when analyzed on reduced SDS-PAGE gels. Her2 is over expressed in cells of many cancer types. It’s over expression is nicely correlated with a poor prognosis of breast and ovarian cancer in patients. ErbB receptors bind to a family of growth factors, termed neuregulins/heregulin (NRG/HRG), which comprise NRG-1, -2, -3, and -4 and include multiple variants. ErbB2/Her2 is an orphan receptor that does not bind ligand alone but heterodimerizes with the other erbB receptors for NRG signaling. Her 2 is a receptor tyrosine kinase with intrinsic tyrosine kinase domain. This new Phospho-Her2 antibody (PHER-240AP) is made against the phospho-Tyrosine containing peptide (aa 1127-1138) from rat Her2 protein.
The Anti-phospho-HER2-selective antibodies were generated against a conserved sequence near the C-terminal that is unique to HER2 protein. The polyclonal antibody strongly labels a 172kDa protein in several breast cancer cells. Anti-phospho-HER2-selective antibody is also available in affinity-purified form for confocal, Western blotting and immunocytochemical analyses. FabGennix Inc. will also conjugate antibodies with fluorescent probes upon request at extra charge. FabGennix, Inc., will also provide Western blot positive controls for Her-201AP and Phospho-Her-240AP antibodies in ready-to-use buffer for easy identification of respective proteins. Limited quantities of antigens are also available. Please inquire for their availability before ordering.
For research use only, not for diagnostic or therapeutic use.
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