A TrkB/insulin receptor-related receptor chimeric receptor induces PC12 cell differentiation and exhibits prolonged activation of mitogen-activated protein kinase

Karen S. Kelly-Spratt, Laura J. Klesse, Jussi Merenmies, Luis F. Parada

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Insulin receptor-related receptor (IRR), an orphan receptor in the insulin receptor (IR) family of receptor tyrosine kinases, is primarily localized to neural crest-derived sensory neurons during embryonic development. Expression of IRR closely resembles that of the nerve growth factor receptor, TrkA. To analyze the signaling properties and function of IRR in PC12 cells, a TrkB/IRR hybrid receptor was used. In contrast to IR activation, brain-derived neurotrophic growth factor-mediated activation of the TrkB/IRR receptor resulted in differentiation rather than proliferation. Analysis of cytoplasmic substrates activated by the TrkB/IRR receptor indicates a signaling pathway similar to that of the IR. Mutagenesis studies further show that only TrkB/IRR receptors able to phosphorylate mitogen- activated protein kinase elicit a differentiation response. Our analysis indicates that prolonged kinetics of mitogen-activated protein kinase activation mediated by the TrkB/IRR chimeric receptor correlates with induction to differentiate.

Original languageEnglish (US)
Pages (from-to)805-812
Number of pages8
JournalCell Growth and Differentiation
Volume10
Issue number12
StatePublished - Dec 1999

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trkB Receptor
PC12 Cells
Mitogen-Activated Protein Kinases
Cell Differentiation
Insulin Receptor
Nerve Growth Factor Receptor
insulin receptor-related receptor
Neural Crest
Brain-Derived Neurotrophic Factor
Receptor Protein-Tyrosine Kinases
Sensory Receptor Cells
Mutagenesis
Embryonic Development

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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A TrkB/insulin receptor-related receptor chimeric receptor induces PC12 cell differentiation and exhibits prolonged activation of mitogen-activated protein kinase. / Kelly-Spratt, Karen S.; Klesse, Laura J.; Merenmies, Jussi; Parada, Luis F.

In: Cell Growth and Differentiation, Vol. 10, No. 12, 12.1999, p. 805-812.

Research output: Contribution to journalArticle

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