Epidermal growth factor (EGFR) is a founding member of the erbB family of receptor tyrosine kinases structurally related four. In humans, (noise, of ErbB2) HER1 (EGFR, ERBB1), of Her2, (of ErbB3) HER3, and this will contain the (of ErbB4) HER4. Erythroid leukemia virus oncogene: gene symbol, the ErbB receptors, these receptors is determined by the name of the cancer gene of the virus has been in homology. For example, ErbB signaling insufficient in humans is associated with the development of neurodegenerative disorders multiple sclerosis and Alzheimer’s disease and other. In mice, the loss of signal from each member of the ErbB family result of embryonic death and defects, of organs, including lung, skin, brain and heart. ErbB signaling excessive, is associated with the development of a wide range of types of solid tumors. The ErbB-2 with ErbB-1 of, is found in many human cancers, excessive signaling of those may be an important factor in the development of andmalignancy of these tumors.

ErbB receptors are composed of the extracellular domain or the extracellular domain comprises a cytoplasmic region containing tyrosine and kinasedomain transmembrane of about 620 amino acids. , “L” extracellular domain of each member of the family consists of CR2 sub-domains of the four is an area “CR” cysteine-rich and leucine-rich repeat domain, and L1, CR1, L2,. (L2), and sub-domains of these are shown in red (CR2) (CR1), yellow (L1), green blue in the figure below. These domains, is the domain of I-IV, respectively. Four members of the erbB family of protein growth factors that activate ErbB receptors ligands.There 11 which can form oligomers higher homodimer start of a subset of growth factors potential, perhaps more and heteroaryl is. Ability of growth factors each for the activation of the ErbB receptor is presented in the following table, – means that it is not possible to activate the ErbB receptors by a respective and capabilities.

If that is not bound to a ligand, the extracellular domain of ErbB-1 -4 and -3, structure of “ties” can mediate interactions hand the monomers dimerization amino acids in length 10, can be found in. In contrast, the dimerization arm is attached, as a dimer and possible interactions monomers, the monomers, ErbB-2 non-ligand and ErbB-1 which was bound to the ligand surface receptors It is exposed to the body. A result of the dimerization ectodomain, as there is the positioning of the cytoplasmic domain of two, of specific tyrosine, serine, threonine, and the phosphoric acid transition, can occur in the cytoplasmic domain of each ErbB receptors at the amino acid. Of specific tyrosine 10 has been identified in ErbB-1 cytoplasm 7 2 threonine and serine, at least these dephosphorylated with dimerization of the receptor, in some cases, it may be phosphorylated. The number of phosphorylation sites a potential is present in dimer two or more single or multiple of these sites, it is phosphorylated at any given time.

Of ErbB-1 is overexpressed in many types of cancer. Drug panitumumab, cetuximab, gefitinib and erlotinib, is used to inhibit such. In recent years, it may be associated with enhancement of ErbB receptor -3 has been shown resistance gefitinib and cetuximab was acquired. This is associated with the overexpression acquisition of c-Met ErbB-3, phosphorylation to activate the Akt pathway in the order. ErbB-2 (HER-2) in, is overexpressed in breast cancer frequently. Drug trastuzumab (Herceptin) is targeted to this receptor. It was not known whether the cause resistance to Trastuzumab recently and one-third of women only support trastuzumab. This, that it may benefit more from drugs that inhibit the PI3K/AKT molecular pathway is actually compared to breast cancer patients with ER is displayed.

ErbB receptor tyrosine kinases, have been developed as an important regulatory parties to allow the extracellular environment to communicate with machinery for intracellular delivery of appropriate biological response to changes in the environment far . Since its discovery, many aspects of the erbB family, is designed with an emphasis on aberration of signaling in human disease. However, only now, in the presence of atomic coordinates of these receptors, the person will be able to build a complete model of the mechanism of subsequent activation of tyrosine kinase and dimerization of ligand-induced receptor. Furthermore, coupled with the realization of the point of view of systems biology, the recent introduction of new high-throughput screening method, to clarify the huge complexity of the network to allow the evolution and possible stable signal. This knowledge may affect the position of the disease and systemic shock like this, such as resistance to ErbB targeted therapies as an act of resistance.

We present the crystal structure at 2.5 resolution of bind truncated human EGFR extracellular domain to TGFα. You interact with the contact with the main chain of many of the L1 and L2 through interaction with residues L2 domain of L1 and TGFαEGFR, were key save. The results, EGFR family members shows how that can be connected to the family of ligand of very volatile. In the case of a 02 minute TGFα2 time: a sEGFR501 complex, each ligand reacts with the receptor molecule. There are two types of dimer in the asymmetric unit: head dimer – comprising contacting the back-to-back dimer while being controlled by the interaction of CR1 domain between the receptor and the L2 domain and L1, head. Based on the mutagenesis experiment embedded sequence conservation, and surface, dimer of back-to-back, is a favorite of organic matter.

Family (also known as ErbB receptor Further EGFR,) epidermal growth factor and insulin receptor (IR), the composition of the extracellular domain are similar. You’ve seen the structure that has been established for the whole family, including a complex and some monoclonal antibody fragment or EGFR ligands in the past five years. These structures, has led to a clear understanding of the mechanism of inhibition and activation. On the other hand, corresponds understanding behind the IR family. However, in recent years, the conformation extracellular region of the receptor, the structure of both the complete extracellular domain and a portion of the IR is published and shows that it has adopted a “V inverted” unexpected to the cell membrane are. It has very different bending of the EGFR this is not activated and (tether) conformation, and provides insight into the potential mechanisms of activation of the IR.

Is the prototype (HER) family of ErbB receptors (the RTK) receptor tyrosine kinases that regulate cell growth and differentiation, epidermal growth factor (EGF) receptor, have been implicated in many human cancers. By inducing dimerization of the 621 amino acid EGF receptor extracellular domain, EGF activates its receptor. We describe the crystal structure of 2.8 resolution extracellular region of the entire (sEGFR) in the non-activated state. Structure, to clarify the autoinhibited set is blocked by intermolecular interaction completely dimerization interface in the active structure sEGFR recently. To turn on the EGF receptor binding, it should promote the rearrangement of a large domain to publish this dimerization interface. It offers a new approach to the design of the ErbB receptor antagonist with full contrast in the activation of the RTK of other mechanisms.

We also, we determined the 3.2-ray crystal structure of the extracellular domain of (HER2 or ErbB2) human epidermal growth factor receptor 2, a complex antigen-binding fragment of Pertuzumab, a monoclonal antibody anti-ErbB2 known as OMNITARG or 2C4 . Pertuzumab binds near the center of ErbB2 of steric hindrance of the binding pocket required for signaling and dimer domain II, and receptor. Of ErbB2 – The pertuzumab structure, which defines the essential pertuzumab residues for interaction of ErbB2 in combination with the data of previous mutagenesis. To analyze the side interface of ErbB2, and the contact number of pertuzumab mutant residues, we examined the effect of these mutations on the hetero-ErbB3 ErbB2 binding and parts of Mab’s. Conserved residues that we also are required for homodimerization of EGF receptor previously been shown showed that it can be released for the hetero-ErbB3 in ErbB2.