NRG1

The most thoroughly examined neuregulin is NRG1, the neu differentiation factor (also heregulin, glial growth factor, or acetylcholine receptor-inducing activity) (MIM.142445).

NRG1 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 not shown in this illustration. Heterodimers of ERBB3 and ERBB2, which has no direct ligand, are potent in causing cell transformation.

Controlled levels of signaling through ERBBs 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 degredation. Infact the rate of degredation is dependent on factors that appear to act independent of ligand binding.

Nrdp-1 (Neuroregulin receptor degradation protein-1) is one such protein. Ndrp-1 is an E3 ubiqitin ligase that tags ErbB3 for degredation in non-lysosomal compartments. The cycling of ErbB1 is similar to that of EGF receptor and is included for contrast. The EGFR cycling is illustrated on the CBL Pathway.

See also

 NRGs