PMID: 18187921Jan 12, 2008Paper

Effect of synthetic cell-penetrating peptides on TrkA activity in PC12 cells

Journal of Pharmacological Sciences
Munetaka HiroseYoshifumi Tanaka

Abstract

As TrkA, a high-affinity receptor of nerve growth factor (NGF), is a potential target for relieving uncontrolled inflammatory pain, an effective inhibitor of TrkA has been required for pain management. To identify a specific inhibitor of TrkA activity, we designed cell-penetrating peptides combined with amino-acid sequences in the activation loop of TrkA to antagonize tyrosine kinase activity. To select a peptide inhibiting TrkA activity, we examined the effect of cell-penetrating peptides on tyrosine kinase activity of recombinant TrkA in vitro and studied their effects on NGF-stimulated neurite outgrowth and protein phosphorylation in PC12 cells. Thereafter we investigated the effect of the selected peptide on NGF-stimulated TrkA activity and the expression of transient receptor potential channel 1 in PC12 cells. The selected peptide inhibited TrkA activity, but did not inhibit tyrosine kinase activities of other receptor-type tyrosine kinases in vitro. It also suppressed NGF-stimulated responses in PC12 cells. The selected synthetic cell-penetrating peptide antagonizing TrkA function would be a candidate for inflammatory pain therapy.

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Citations

Apr 25, 2012·Cellular and Molecular Life Sciences : CMLS·John HowlSarah Jones
May 24, 2012·Journal of Anesthesia·Mari TabataMunetaka Hirose
Jul 12, 2013·Biotechnology Journal·Monika LukanowskaSarah Jones
Aug 17, 2010·Journal of Pharmacological Sciences·Wei-Ying MaMunetaka Hirose
Oct 12, 2019·Artificial Cells, Nanomedicine, and Biotechnology·Niansheng Liu, Mingfu Fan
Jun 18, 2014·Menopause : the Journal of the North American Menopause Society·David R Walega, Pauline Maki
Oct 10, 2015·Pain Practice : the Official Journal of World Institute of Pain·Munetaka HiroseEri Murata

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