• Purity

  >95%, by SDS-PAGE under reducing conditions and visualized by silver stain

• Endotoxin Level

  <0.01 EU per 1 μg of the protein by the LAL method.  

• Activity

  Measured in a serum-free cell proliferation assay using MCF?7 human breast cancer cells. Karey, K.P.     et al. (1988) Cancer Research     48:4083. The ED    ₅₀ for this effect is 20?100 ng/mL.

• Source

  Mouse myeloma cell line, NS0-derived Ser20-Lys241, with a C-terminal 6-His tag

• Accession #

• N-terminal Sequence    
  Analysis

  Ser20

• Predicted Molecular Mass

  24.8 kDa

• SDS-PAGE

  40-43 kDa, reducing conditions

Background: Neuregulin-1/NRG1

Neuregulin-1 (NRG1) belongs to a family of structurally related glycoproteins encoded by four distinct but related genes,   Nrg1, Nrg2,   Nrg3,   and Nrg4. Through alternative splicing or the use of alternative promoters,   Nrg1 encodes more than 14 soluble or transmembrane proteins. Type I NRG1 isoforms include Neu Differentiation Factor, Heregulin, and ARIA. These consist of an N-terminal domain, an Ig-like domain, a linker with a Ser/Thr rich region, an EGF-like domain, a transmembrane segment, and a cytoplasmic domain. Type II isoforms such as Glial Growth Factor have a larger N-terminal domain and lack the Ser/Thr rich linker. Type III isoforms such as Sensory and Motor neuron-Derived Factor lack the Ig-like domain but contain a cysteine rich domain (CRD) and a second transmembrane segment (1 - 5). The alpha and beta splice variants of NRG1 differ in their extracellular juxtamembrane regions (3, 6). This recombinant protein corresponds to the extracellular domain (ECD) of the type I alpha isoforms (Accession # Q7RTV8). NRG1 isoforms exhibit distinct expression patterns and functions (7). The EGF-like domain, which is common to all NRG1 isoforms, is required for Neuregulin binding to ErbB3 or ErbB4 receptors (3). ErbB3 or ErbB4 subsequently heterodimerize with ErbB2, resulting in tyrosine phosphorylation and NRG1 induced signaling (1, 2). Soluble growth factors can be released by TACE/ADAM17, BACE, or ADAM19 mediated shedding of the ECD of transmembrane NRG1 (8 - 10). The cytoplasmic region can be cleaved by gamma -secretase, generating a repressor that inhibits the transcription of proapoptotic genes (11). NRG1 regulates multiple nervous system functions including axon guidance, synapse formation and plasticity, glial cell development, and axon myelination (1, 2). In the heart, NRG1 regulates organ morphogenesis and contractility and also plays a cardioprotective role following tissue injury (12). Multiple polymorphisms and aberrant expression of NRG1 isoforms are associated with the development of schizophrenia and many cancers (1, 2, 13).

• References:

1. Mei, L. and W.-C. Xiong (2008) Nat. Rev. Neurosci. 9:437.

2. Talmage, D.A. (2008) Novartis Found. Symp. 289:74.

3. Holmes, W.E. et al. (1992) Science 256:1205.

4. Marchionni, M.A. et al. (1993) Nature 362:312.

5. Ho, W.-H. et al. (1995) J. Biol. Chem. 270:14523.

6. Wen, D. et al. (1994) Mol. Cell. Biol. 14:1909.

7. Meyer, D. et al. (1997) Development 124:3575.

8. Hu, X. et al. (2006) Nat. Neurosci. 9:1520.

9. Willem, M. et al. (2006) Science 314:664.

10. Yokozeki, T. et al. (2007) Genes Cells 12:329.

11. Bao, J. et al. (2003) J. Cell Biol. 161:1133.

12. Lemmens, K. et al. (2007) Circulation 116:954.

13. Breleux, M. (2007) Cell. Mol. Life Sci. 64:2358.

• Entrez Gene IDs:

  3084 (Human); 211323 (Mouse); 112400 (Rat)

• Alternate Names:

  ARIA; GGF2; GGFglial growth factor; Heregulin-1; HGL; HGLneu differentiation factor; HRG; HRG1; HRG1-alpha; HRG1-beta 1; HRGAneuregulin 1 type IV beta 1a; MST131; MSTP131; NDFheregulin, alpha (45kD, ERBB2 p185-activator); neuregulin 1 type IV beta 3; neuregulin 1; Neuregulin1; Neuregulin-1; NRG1; pro-neuregulin-1, membrane-bound isoform; pro-NRG1; sensory and motor neuron derived factor; SMDF