Multiple Levels for Regulation of TrkA in PC12 Cells by Nerve Growth Factor

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<jats:p><jats:bold>Abstract:</jats:bold> TrkA is a receptor tyrosine kinase for nerve growth factor (NGF). Recent studies indicate that NGF regulates not only activation of trkA kinase but also expression of the <jats:italic>trkA</jats:italic> gene. To further define NGF actions on trkA, we examined binding and signaling through trkA after both short and long intervals of NGF treatment. Induction of tyrosine phosphorylation on gp140<jats:sup><jats:italic>trkA</jats:italic></jats:sup> was rapidly followed by down‐regulation of cell surface and total cellular gp140<jats:sup><jats:italic>trkA</jats:italic></jats:sup>. At later intervals, increased expression of trkA was evident in increased mRNA and protein levels. At 7 days, there was increased binding to gp140<jats:sup><jats:italic>trkA</jats:italic></jats:sup> and increased signaling through this receptor. NGF appears to regulate trkA at several levels. In neurons persistently exposed to NGF, maintenance of NGF signaling may require increased <jats:italic>trkA</jats:italic> gene expression.</jats:p>

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