Search results for: Phospho CREB S133 Antibody
#30248305 2018/09/22 To Up
Muscarinic receptor antagonists activate ERK-CREB signaling to augment neurite outgrowth of adult sensory neurons.
A major cellular effector activated by G protein coupled receptors is extracellular signal-regulated kinase (ERK). The ERK signaling cascade regulates a variety of cellular processes including growth and proliferation. Both G protein and β-arrestin-mediated signaling lead to ERK activation by phosphorylation through different kinases. Recently, we have shown muscarinic acetylcholine type 1 receptor (MR) antagonists, muscarinic toxin 7 (MT7) and pirenzepine, elevated neurite outgrowth and protected from small and large fiber neuropathy in adult sensory neurons in various animal models. Thus, we tested the novel hypothesis that muscarinic antagonists could drive neurite outgrowth through altered MR-ERK signaling. We have used two dimensional isoelectric focusing/SDS-PAGE combined with analysis using multiple phospho-epitope specific antibodies to study ERK1/2 phosphorylation and activation of its downstream nuclear effector cyclic response element binding protein (CREB). Activated CREB is known to exhibit neuroprotective and growth promoting effects. One hour of treatment with MT7 and pirenzepine activated ERK through MR and induced a significant increase in levels of pCREB(S133) in cultured sensory neurons. Further, pharmacological blockade or siRNA based knockdown of ERK abolished the MT7 and pirenzepine mediated neuritogenic effect. In addition, we have shown drug-induced alterations of charged protein fractions that may possess additional post-translationally modified forms of ERK and CREB. For the first time we show that long-term treatment, e.g. 1 h, with muscarinic antagonists selective or specific for MR can activate a biased β-arrestin dependent ERK-CREB signal cascade. Our study gives novel insight into muscarinic antagonist-mediated modulation of MR-ERK-CREB signaling which could be exploited for therapy in neuropathic diseases.Mohammad Golam Sabbir, Paul Fernyhough
2473 related Products with: Muscarinic receptor antagonists activate ERK-CREB signaling to augment neurite outgrowth of adult sensory neurons.
96T4200ul50 µg100 100 ug/vial100.00 ug2 Pieces/Box50 100 2 Pieces/Box100 μgRelated Pathways
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