Localisation of Neuregulin 1-β3 to different sub-nuclear structures alters gene expression

Journal article


Wang, M., Trim, C. and Gullick, W. 2011. Localisation of Neuregulin 1-β3 to different sub-nuclear structures alters gene expression. Experimental Cell Research. 317 (4), pp. 423-432. https://doi.org/10.1016/j.yexcr.2010.11.009.
AuthorsWang, M., Trim, C. and Gullick, W.
Abstract

Neuregulins are growth factors that signal via the ErbB3 and ErbB4 receptors. Here we show using immunohistochemistry that they are often expressed in the nucleus of a range of tumour types including soft tissue and breast. The Neuregulin 1 type I-β3 (NRG1-β3) isoform localises to two sub-nuclear compartments in animal cells, nucleoli and spliceosomes. We used NRG1-β3 tagged with photoactivatable GFP and demonstrated that this re-localised from nucleoli to spliceosomes over 90 min. Tyrosine kinase activity was not required for retaining the NRG1-β3 within the nucleus. Mutation of the lysines 14 and 16 or 15 and 16 together prevented nucleolar uptake while four positively charged residues were identified which were required for spliceosome uptake. Molecular modelling suggests that three of these may form a binding site. We showed using a kinome array that NRG1-β3 and a mutant exclusively localising to spliceosomes increased phosphorylation and/or expression of the HER4 and HER2 receptors. Using a transcriptomic analysis the same two constructs induced expression of several messenger RNAs and we confirmed the increased expression at the protein level of the most highly induced, Heat Shock Protein 70B'. These results suggest that Neuregulin activates receptor signalling in spliceosomes leading to altered gene expression.

Year2011
JournalExperimental Cell Research
Journal citation317 (4), pp. 423-432
PublisherElsevier
ISSN0014-4827
Digital Object Identifier (DOI)https://doi.org/10.1016/j.yexcr.2010.11.009.
Publication dates
Print15 Feb 2011
Publication process dates
Deposited15 Jul 2015
Accepted2011
Output statusPublished
Permalink -

https://repository.canterbury.ac.uk/item/87628/localisation-of-neuregulin-1-3-to-different-sub-nuclear-structures-alters-gene-expression

  • 2
    total views
  • 0
    total downloads
  • 0
    views this month
  • 0
    downloads this month

Export as

Related outputs

Kinome scale profiling of venom effects on cancer cells reveals potential new venom activities
Mccullough, D., Atofanei, C., Knight, E., Trim, S. and Trim, C.M. 2020. Kinome scale profiling of venom effects on cancer cells reveals potential new venom activities. Toxicon.
Microbial adaptation to venom is common in snakes and spiders
Esmaeilishirazifard, E., Usher, L., Trim, C., Denise, H., Sangal, V., Tyson, G., Barlow, A., Redway, K., Taylor, J., Kremyda-Vlachou, M., Loftus, T., Lock, M., Wright, K., Dalby, A., Snyder, L., Wuster, W., Trim, S. and Moschos, S. 2018. Microbial adaptation to venom is common in snakes and spiders. bioRxiv. https://doi.org/10.1101/348433v1
Transitioning novel peptide hits into lead compounds
Trim, S. and Trim, C. 2019. Transitioning novel peptide hits into lead compounds. Drug Target Review. (4).
Non-invasive extraction of Cnidarian venom through the use of autotomised tentacles
Robinson, P., Trim, S. and Trim, C. 2019. Non-invasive extraction of Cnidarian venom through the use of autotomised tentacles. Animal Technology and Welfare. 18 (3).
Rapid method for targeted cell (line) selection
Lang, D., Martin, E., Montague, G., O'Malley, C., Root, T., Trim, C., Povey, J., Smales, C. and Racher, A. 2012. Rapid method for targeted cell (line) selection.
Venom: The sharp end of pain therapy
Trim, S. and Trim, C. 2013. Venom: The sharp end of pain therapy. British Journal of Pain. 7 (4), pp. 179-188. https://doi.org/10.1177/2049463713502005
Novel approaches to targeting protein tyrosine kinases
McCullough, D. and Trim, C. 2015. Novel approaches to targeting protein tyrosine kinases. Drug Target Review.
Rapid high-throughput characterisation, classification and selection of recombinant mammalian cell line phenotypes using intact cell MALDI-ToF mass spectrometry fingerprinting and PLS-DA modelling
Povey, J., O'Malley, C., Root, T., Martin, E., Montague, G., Feary, M., Trim, C., Lang, D., Aldread, R., Racher, A. and Smales, C. 2014. Rapid high-throughput characterisation, classification and selection of recombinant mammalian cell line phenotypes using intact cell MALDI-ToF mass spectrometry fingerprinting and PLS-DA modelling. Journal of Biotechnology. 184, pp. 84-93. https://doi.org/10.1016/j.jbiotec.2014.04.028
Neuregulins in the nucleus
McClelland, C. and Gullick, W. 2009. Neuregulins in the nucleus. in: Giordano, A. and Normanno, N. (ed.) Breast Cancer In the Post-Genomic Era Springer. pp. 79-86
Proteomic identification of secreted proteins as surrogate markers for signal transduction inhibitor activity
McClelland, C. and Gullick, W. 2007. Proteomic identification of secreted proteins as surrogate markers for signal transduction inhibitor activity. British Journal of Cancer. 96 (2), pp. 284-289. https://doi.org/10.1038/sj.bjc.6603544
99mTc-SnF2 colloid “LLK”: particle size, morphology, and leukocyte labelling behaviour
McClelland, C., Onuegbulem, E., Carter, N., Leahy, M., O'Doherty, M., Pooley, F., O'Doherty, T., Newsam, R., Ensing, G. and Blower, P. 2003. 99mTc-SnF2 colloid “LLK”: particle size, morphology, and leukocyte labelling behaviour. Nuclear Medicine Communications. 24 (2), pp. 191-202. https://doi.org/10.1097/01.mnm.0000057333.59072.1c
Identification of surrogate markers for determining drug activity using proteomics
McClelland, C. and Gullick, W. 2003. Identification of surrogate markers for determining drug activity using proteomics. Biochemical Society Transactions. 31 (6), pp. 1488-1490. https://doi.org/10.1042/bst0311488