||Monoclonal EGFR antibody specific for Human EGFR for use in ELISA and Western Blot.
Epidermal growth factor receptor (EGFR) is a 170 kDa transmembrane receptor tyrosine kinase. EGFR protein was first identified as a binding partner of EGF. In addition, there are six other different ligands that can bind EGFR; transforming growth factor alpha (TGF alpha or TGFa), epiregulin (EPR), amphiregulin (AR), heparin binding EGF (HBEGF), betacellulin (BTC), and epigen. These ligands control downstream signaling pathways, such as proliferation, survival, differentiation, and migration, and when they bind to the EGFR causing it to dimerize and become activated. Modulation of receptor trafficking and degradation are essential for proper EGFR signaling, and EGFR trafficking studies have primarilty been performed using EGF as the ligand. As a result, the majority of research is focused on examining EGF/EGFR interactions and how they regulate its recycling and degradation, and there is a scarcity of information on how EGFR interacts with its other important ligand partners. When EGFR binds to its cognate ligand EGF, this induces tyrosine phosphorylation and receptor dimerization with other family members leading to enhanced uncontrolled proliferation, which is a major cancer causing signalling pathway.
||High expression of EGFR has been reported in a variety of epithelial tumors. EGFR is present in cell membranes and is also secreted from the cell. Specifically it is found in Nuclear membranes, Endoplasmic reticulum membranes, Golgi apparatus membranes, Endosomal membranes and is also secreted through endosomes. Upon EGF binding, EGFR is translocated from the cell membrane to the nucleus via Golgi and ER. Once dimerization occurs and it is activated, it is then endocytosed from the cell.
|Implications in Disease
||The overexpression of EGFR in various epithelial tumors was widely reported and it has been substantiated that deregulation of EGFR itself and its signaling pathways an important role in human cancers. Epidermal growth factor receptors (EGFRs) are a large family of receptor tyrosine kinases (TK) expressed in several types of cancer, including breast, lung, esophageal, and head and neck. Distinct therapeutic approaches currently employed for targeting EGFR in various human malignancies are the use of monoclonal antibodies and small molecule tyrosine kinase inhibitors.
||Belongs to the protein kinase superfamily. It contains a catalytic domain of protein tyrosine kinase at amino acids 659-974; a transmembrane domain at amino acids 589-632; and a number of polypeptide binding domains. It also contains a number of Furin-like repeats. Cysteine rich region. Exact function of the domain is not known. Furin is a serine-kinase dependent proprotein processor. Other members of this family include endoproteases and cell surface receptors.
||Src phosphorylates EGFR on tyrosine 845 (Y845) in the Src-EGFR complex. Y845 of EGFR is located in the activation segment of the kinase domain, where many protein kinases contain kinase-activating autophosphorylation sites (e.g., cAMP-dependent protein kinase, Src family kinases, transmembrane receptor type tyrosine kinases) or trans-phosphorylation sites (e.g., cyclin-dependent protein kinase, mitogen-activated protein kinase, Akt protein kinase). A number of studies have demonstrated that Y845 phosphorylation serves an important role in cancer as well as normal cells. It is evident that binding of EGF to EGFR triggers a series autophosphorylation events of specific tyrosine residues (for example Tyr 1045, Tyr 992, Tyr 975, Tyr 1068, Tyr 1173 etc) in its kinase domain i.e activated EGFR protein level will be elevated without changing total EGFR protein level. Methylation at Arg-1199 by PRMT5 positively stimulates phosphorylation at Tyr-1197.
||Entrez Gene: 1956 Human, Omim: 131550 Human, SwissProt: P00533 Human, Unigene: 488293 Human