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  • Title: Deletion of a conserved juxtamembrane sequence in Trk abolishes NGF-promoted neuritogenesis.
    Author: Peng X, Greene LA, Kaplan DR, Stephens RM.
    Journal: Neuron; 1995 Aug; 15(2):395-406. PubMed ID: 7646892.
    Abstract:
    Deletion of a conserved juxtamembrane sequence (KFG) in the Trk NGF receptor resulted in impaired neurite outgrowth, somatic hypertrophy, and induction of c-fos, c-jun, and TIS1 immediate-early genes. In contrast, these receptors retained the ability to mediate NGF-promoted survival and TIS8 and TIS11 immediate-early gene induction. The mutated receptor also mediated unimpaired autophosphorylation; SHC, PLC-gamma 1, and ERK tyrosine phosphorylation; and PI-3 kinase and ERK activation. However, SNT protein tyrosine phosphorylation, which wild-type receptors mediate via a ras-independent pathway, was undetectable. These findings indicate that the KFG sequence is indispensable for activating a ras-independent NGF signaling pathway involved in promoting neuronal differentiation and highlight potential roles of non-tyrosine-containing receptor domains in growth factor signal transduction.
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