Analysis Note

The bioactivity is tested in culture using a proliferation assay with the human cell line MCF-7.

Biochem/physiol Actions

Heregulin (HRG) is the human homologue to the neu differentiation factor (NDF) in rat. The heregulin family members contain one EGF-like motif and an IgD-like motif in the extracellular domain. They bind to ErbB-2, ErbB-3, and ErbB-4 (receptors closely related to EGFR). HRG-α and HRG-β isoforms differ slightly in the EGF domain due to alternate splicing. HRG-β isoforms are further subdivided into β1, β2, and β3 isoforms, which show identical binding and activation characteristics. Both α and β HRG isoforms bind to ErbB-3 and ErbB-4 homodimers, but not directly to ErbB-2. HRG-α binding to ErbB-3 and ErbB-4 is reported to be approximately 100-fold weaker than that of HRG-β. When ErbB-2 is combined into a heterodimer with ErbB-3 or ErbB-4, the binding affinities of both α and β isoforms are substantially improved. HRGs are mitogenic for Schwann cells in culture and weakly to moderately mitogenic for a variety of epithelial cells, including mammary, ovarian, lung, and gastric cells. HRGs inhibit proliferation and induce differentation in some tumor cell lines, such as certain mammary tumor cells, which are arrested at the G2M phase. HRGs also induce expression of acetylcholine receptors and possibly other molecules in muscle cells at newly formed neuromuscular synapses, suggesting they may play a role in neuromuscular synapse maturation and maintenance.

Physical form

Lyophilized from a 0.2 µm filtered solution in phosphate buffered saline, pH 7.4, containing 50 µg bovine serum albumin per 1 µg as a carrier protein.