Staurosporine causes epidermal growth factor to induce differentiation in PC12 cells via receptor up-regulation.

The Journal of Biological Chemistry
S Raffioni, R A Bradshaw

Abstract

Although they all utilize tyrosine kinase receptors and activate signaling pathways characterized by a similar set of phosphoproteins, epidermal growth factor (EGF) promotes only cell division while fibroblast growth factor (FGF) and nerve growth factor (NGF) can induce division followed by differentiation in PC12 cells. EGF, in contrast to NGF and FGF, cannot maintain the sustained phosphorylation and activation of mitogen-activated protein (MAP) kinase kinase and MAP kinases, which may account for the difference in phenotypic response. The pretreatment of PC12 cells with staurosporine, a protein kinase inhibitor, causes a substantial increase in both receptor and MAP kinase phosphorylation that results in a differentiative response (neurite proliferation). However, neurites begin to disappear after 3 days, despite the continual presence of EGF, and are largely gone after 5 days, which is not the case with NGF and FGF. Thus, the effect of staurosporine is not permanent. Northern and Western blots indicate that the staurosporine response mainly results from a substantial up-regulation in EGF receptor synthesis, thus providing a much stronger cell surface signal and supporting the view that quantitative rather than qualitative d...Continue Reading

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Citations

Feb 13, 2001·American Journal of Physiology. Lung Cellular and Molecular Physiology·P M LindroosJ C Bonner
Oct 27, 2011·Molecular & Cellular Proteomics : MCP·Jordane BiarcRalph A Bradshaw
Jul 21, 1995·The Journal of Biological Chemistry·J D RamamoorthyV Ganapathy
Mar 5, 2003·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Darren R TysonRalph A Bradshaw
Nov 5, 2004·The European Journal of Neuroscience·Yona GoldshmitAnn M Turnley

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