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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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1-Phosphatidylinositol 4-Kinase
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Adaptor Proteins, Signal Transducing*
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Adaptor Proteins, Vesicular Transport*
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Amino Acid Sequence
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Animals
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism
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Cell Size
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Culture Media, Serum-Free
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Isoenzymes / metabolism
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Molecular Sequence Data
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Mutagenesis, Site-Directed
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Nerve Growth Factors / pharmacology*
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Nerve Tissue Proteins / metabolism*
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Neurites / drug effects*
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Neurites / physiology
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Neurites / ultrastructure
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PC12 Cells
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Phospholipase C gamma
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Phosphorylation
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Phosphotransferases (Alcohol Group Acceptor) / metabolism
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Protein Processing, Post-Translational
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Proteins / metabolism
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Proto-Oncogene Proteins / chemistry
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Proto-Oncogene Proteins / genetics*
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Proto-Oncogene Proteins / physiology
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Rats
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Receptor Protein-Tyrosine Kinases / chemistry
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Receptor Protein-Tyrosine Kinases / genetics*
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Receptor Protein-Tyrosine Kinases / physiology
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Receptor, trkA
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Receptors, Nerve Growth Factor / chemistry
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Receptors, Nerve Growth Factor / genetics*
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Receptors, Nerve Growth Factor / physiology
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Sequence Deletion*
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Shc Signaling Adaptor Proteins
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Signal Transduction
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Src Homology 2 Domain-Containing, Transforming Protein 1
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Type C Phospholipases / metabolism
Substances
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Adaptor Proteins, Signal Transducing
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Adaptor Proteins, Vesicular Transport
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Culture Media, Serum-Free
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Isoenzymes
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Nerve Growth Factors
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Nerve Tissue Proteins
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Proteins
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Proto-Oncogene Proteins
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Receptors, Nerve Growth Factor
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Shc Signaling Adaptor Proteins
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Shc1 protein, rat
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Src Homology 2 Domain-Containing, Transforming Protein 1
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Phosphotransferases (Alcohol Group Acceptor)
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1-Phosphatidylinositol 4-Kinase
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Receptor Protein-Tyrosine Kinases
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Receptor, trkA
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Calcium-Calmodulin-Dependent Protein Kinases
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Type C Phospholipases
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Phospholipase C gamma