RGD Reference Report - Neuregulin signaling on glucose transport in muscle cells. - Rat Genome Database
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Neuregulin signaling on glucose transport in muscle cells.

Authors: Canto, C  Suarez, E  Lizcano, JM  Grino, E  Shepherd, PR  Fryer, LG  Carling, D  Bertran, J  Palacin, M  Zorzano, A  Guma, A 
Citation: Canto C, etal., J Biol Chem. 2004 Mar 26;279(13):12260-8. Epub 2004 Jan 6.
RGD ID: 2289958
Pubmed: (View Article at PubMed) PMID:14711829
DOI: Full-text: DOI:10.1074/jbc.M308554200

Neuregulin-1, a growth factor that potentiates myogenesis induces glucose transport through translocation of glucose transporters, in an additive manner to insulin, in muscle cells. In this study, we examined the signaling pathway required for a recombinant active neuregulin-1 isoform (rhHeregulin-beta(1), 177-244, HRG) to stimulate glucose uptake in L6E9 myotubes. The stimulatory effect of HRG required binding to ErbB3 in L6E9 myotubes. PI3K activity is required for HRG action in both muscle cells and tissue. In L6E9 myotubes, HRG stimulated PKBalpha, PKBgamma, and PKCzeta activities. TPCK, an inhibitor of PDK1, abolished both HRG- and insulin-induced glucose transport. To assess whether PKB was necessary for the effects of HRG on glucose uptake, cells were infected with adenoviruses encoding dominant negative mutants of PKBalpha. Dominant negative PKB reduced PKB activity and insulin-stimulated glucose transport but not HRG-induced glucose transport. In contrast, transduction of L6E9 myotubes with adenoviruses encoding a dominant negative kinase-inactive PKCzeta abolished both HRG- and insulin-stimulated glucose uptake. In soleus muscle, HRG induced PKCzeta, but not PKB phosphorylation. HRG also stimulated the activity of p70S6K, p38MAPK, and p42/p44MAPK and inhibition of p42/p44MAPK partially repressed HRG action on glucose uptake. HRG did not affect AMPKalpha(1) or AMPKalpha(2) activities. In all, HRG stimulated glucose transport in muscle cells by activation of a pathway that requires PI3K, PDK1, and PKCzeta, but not PKB, and that shows cross-talk with the MAPK pathway. The PI3K, PDK1, and PKCzeta pathway can be considered as an alternative mechanism, independent of insulin, to induce glucose uptake.


Gene Ontology Annotations    

Biological Process

Molecular Function

Molecular Pathway Annotations    
Objects Annotated

Genes (Rattus norvegicus)
Erbb3  (erb-b2 receptor tyrosine kinase 3)

Genes (Mus musculus)
Erbb3  (erb-b2 receptor tyrosine kinase 3)

Genes (Homo sapiens)
ERBB3  (erb-b2 receptor tyrosine kinase 3)

Additional Information