| Health / Medical Topics |
ErbB3 Receptor Recycling Pathway
The neuregulins comprise a subfamily of at least four epidermal growth factor (EGF)-like growth factors that influence a variety of cellular events, including proliferation, differentiation, migration, survival, and fate. The most thoroughly examined neuregulin, neu differentiation factor NDF (AKA: neuregulin-1; NRG1; also heregulin, glial growth factor, or acetylcholine receptor-inducing activity), has been shown to play essential roles in the development of cardiac and neural tissues and also has been shown to play a role in the postsynaptic development of the neuromuscular junction. The neuregulins bind to ErbB3 or ErbB4 and can activate the ErbB2 receptor through a heterodimerization mechanism. Heterodimers of ErbB3 and ErbB2, which has no direct ligand, are potent in causing cell transformation. Controlled levels of signaling through ErbB and other growth factor receptors are maintained by keeping a relatively limited amount of receptors at the cell surface. Receptor overexpression can lead to disease states such as the genesis or progression of tumors. Hence, mechanisms must exist for localizing and maintaining a precise concentration of growth factor receptors at the site of signal reception. ErbB2, ErbB3, and ErbB4 are somewhat unique among studied receptor tyrosine kinases in that they exhibit impaired ligand-induced internalization, down-regulation, and degradation. In fact, the rate of degradation is dependent on factors that appear to act independent of ligand binding. Nrdp-1 (Neuregulin receptor degradation protein-1) is one such protein. Ndrp-1 is an E3 ubiquitin ligase that tags ErbB3 for degradation in non-lysosomal compartments. The cycling of ErbB1 is similar to that of EGF receptor and is included for contrast. (NCI Thesaurus/BIOCARTA)
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