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ErbB
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ErbB
The ErbB family of proteins contains four receptor tyrosine kinases, structurally related to the epidermal growth factor receptor (EGFR), its first discovered member. In humans, the family includes Her1 (EGFR, ErbB1), Her2 (ErbB2), Her3 (ErbB3), and Her4 (ErbB4). The gene symbol, ErbB, is derived from the name of a viral oncogene to which these receptors are homologous: erythroblastic leukemia viral oncogene. Insufficient ErbB signaling in humans is associated with the development of neurodegenerative diseases, such as multiple sclerosis and Alzheimer's disease, while excessive ErbB signaling is associated with the development of a wide variety of types of solid tumor.
ErbB protein family signaling is important for development. For example, ErbB-2 and ErbB-4 knockout mice die mid-gestation due to deficient cardiac function associated with a lack of myocardial ventricular trabeculation and display abnormal development of the peripheral nervous system. In ErbB-3 receptor mutant mice, they have less severe defects in the heart and thus are able to survive longer throughout embryogenesis. Lack of Schwann cell maturation leads to degeneration of motor and sensory neurons. Excessive ErbB signaling is associated with the development of a wide variety of types of solid tumor. ErbB-1 and ErbB-2 are found in many human cancers, and their excessive signaling may be critical factors in the development and malignancy of these tumors.
The ErbB protein family consists of 4 members
v-ErbBs are homologous to EGFR, but lack sequences within the ligand binding ectodomain.
All four ErbB receptor family members are nearly same in the structure having single-chain of modular glycoproteins. This structure is made up of an extracellular region or ectodomain or ligand binding region that contains approximately 620 amino acids, a single transmembrane-spanning region containing approximately 23 residues, and an intracellular cytoplasmic tyrosine kinase domain containing up to approximately 540 residues. The extracellular region of each family member is made up of 4 subdomains, L1, CR1, L2, and CR2, where "L" signifies a leucine-rich repeat domain and "CR" a cysteine-rich region, and these CR domains contain disulfide modules in their structure as 8 disulfide modules in CR1 domain, whereas 7 modules in CR2 domain. These subdomains are shown in blue (L1), green (CR1), yellow (L2), and red (CR2) in the figure below. These subdomains are also referred to as domains I-IV, respectively. The intracellular/cytoplasmic region of the ErbB receptor consists mainly of three subdomains: A juxtamembrane with approximately 40 residues, a kinase domain containing approximately 260 residues and a C-terminal domain of 220-350 amino acid residues that become activated via phosphorylation of its tyrosine residues that mediates interactions of other ErbB proteins and downstream signaling molecules.
The figure below shows the tridimensional structure of the ErbB family proteins, using the pdb files 1NQL (ErbB-1), 1S78 (ErbB-2), 1M6B (ErbB-3) and 2AHX (ErbB-4):
The four members of the ErbB protein family are capable of forming homodimers, heterodimers, and possibly higher-order oligomers upon activation by a subset of potential growth factor ligands. There are 11 growth factors that activate ErbB receptors.
The ability ('+') or inability ('-') of each growth factor to activate each of the ErbB receptors is shown in the table below:
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ErbB
The ErbB family of proteins contains four receptor tyrosine kinases, structurally related to the epidermal growth factor receptor (EGFR), its first discovered member. In humans, the family includes Her1 (EGFR, ErbB1), Her2 (ErbB2), Her3 (ErbB3), and Her4 (ErbB4). The gene symbol, ErbB, is derived from the name of a viral oncogene to which these receptors are homologous: erythroblastic leukemia viral oncogene. Insufficient ErbB signaling in humans is associated with the development of neurodegenerative diseases, such as multiple sclerosis and Alzheimer's disease, while excessive ErbB signaling is associated with the development of a wide variety of types of solid tumor.
ErbB protein family signaling is important for development. For example, ErbB-2 and ErbB-4 knockout mice die mid-gestation due to deficient cardiac function associated with a lack of myocardial ventricular trabeculation and display abnormal development of the peripheral nervous system. In ErbB-3 receptor mutant mice, they have less severe defects in the heart and thus are able to survive longer throughout embryogenesis. Lack of Schwann cell maturation leads to degeneration of motor and sensory neurons. Excessive ErbB signaling is associated with the development of a wide variety of types of solid tumor. ErbB-1 and ErbB-2 are found in many human cancers, and their excessive signaling may be critical factors in the development and malignancy of these tumors.
The ErbB protein family consists of 4 members
v-ErbBs are homologous to EGFR, but lack sequences within the ligand binding ectodomain.
All four ErbB receptor family members are nearly same in the structure having single-chain of modular glycoproteins. This structure is made up of an extracellular region or ectodomain or ligand binding region that contains approximately 620 amino acids, a single transmembrane-spanning region containing approximately 23 residues, and an intracellular cytoplasmic tyrosine kinase domain containing up to approximately 540 residues. The extracellular region of each family member is made up of 4 subdomains, L1, CR1, L2, and CR2, where "L" signifies a leucine-rich repeat domain and "CR" a cysteine-rich region, and these CR domains contain disulfide modules in their structure as 8 disulfide modules in CR1 domain, whereas 7 modules in CR2 domain. These subdomains are shown in blue (L1), green (CR1), yellow (L2), and red (CR2) in the figure below. These subdomains are also referred to as domains I-IV, respectively. The intracellular/cytoplasmic region of the ErbB receptor consists mainly of three subdomains: A juxtamembrane with approximately 40 residues, a kinase domain containing approximately 260 residues and a C-terminal domain of 220-350 amino acid residues that become activated via phosphorylation of its tyrosine residues that mediates interactions of other ErbB proteins and downstream signaling molecules.
The figure below shows the tridimensional structure of the ErbB family proteins, using the pdb files 1NQL (ErbB-1), 1S78 (ErbB-2), 1M6B (ErbB-3) and 2AHX (ErbB-4):
The four members of the ErbB protein family are capable of forming homodimers, heterodimers, and possibly higher-order oligomers upon activation by a subset of potential growth factor ligands. There are 11 growth factors that activate ErbB receptors.
The ability ('+') or inability ('-') of each growth factor to activate each of the ErbB receptors is shown in the table below: