Rit mutants confirm role of MEK/ERK signaling in neuronal differentiation and reveal novel Par6 interaction

Jennifer L. Rudolph, Geng Xian Shi, Eda Erdogan, Alan P Fields, Douglas A. Andres

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Rit is a novel member of the Ras superfamily of small GTP-binding proteins that regulates signaling pathways controlling cellular fate determination. Constitutively activated mutants of Rit induce terminal differentiation of pheochromocytoma (PC6) cells resulting in a sympathetic neuron-like phenotype characterized by the development of highly-branched neurites. Rit signaling has been found to activate several downstream pathways including MEK/ERK, p38 MAPK, Ral-specific guanine nucleotide exchange factors (GEFs), and Rit associates with the Par6 cell polarity machinery. In this study, a series of Rit effector loop mutants was generated to test the importance of these cellular targets to Rit-mediated neuronal differentiation. We find that Rit-mediated neuritogenesis is dependent upon MEK/ERK MAP kinase signaling but independent of RalGEF activation. In addition, in vivo binding studies identified a novel mechanism of Par6 interaction, suggesting that the cell polarity machinery may serve to spatially restrict Rit signaling.

Original languageEnglish (US)
Pages (from-to)1793-1800
Number of pages8
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1773
Issue number12
DOIs
StatePublished - Dec 2007

Fingerprint

Cell Polarity
Mitogen-Activated Protein Kinase Kinases
ral Guanine Nucleotide Exchange Factor
MAP Kinase Signaling System
Extracellular Signal-Regulated MAP Kinases
Pheochromocytoma
p38 Mitogen-Activated Protein Kinases
Neurites
GTP-Binding Proteins
Phenotype
Neurons
PC6 extract

Keywords

  • ERK MAP kinase
  • GTPase
  • Neuronal differentiation
  • Par6
  • PC12 cell
  • Ras
  • Rit

ASJC Scopus subject areas

  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

Rit mutants confirm role of MEK/ERK signaling in neuronal differentiation and reveal novel Par6 interaction. / Rudolph, Jennifer L.; Shi, Geng Xian; Erdogan, Eda; Fields, Alan P; Andres, Douglas A.

In: Biochimica et Biophysica Acta - Molecular Cell Research, Vol. 1773, No. 12, 12.2007, p. 1793-1800.

Research output: Contribution to journalArticle

Rudolph, Jennifer L. ; Shi, Geng Xian ; Erdogan, Eda ; Fields, Alan P ; Andres, Douglas A. / Rit mutants confirm role of MEK/ERK signaling in neuronal differentiation and reveal novel Par6 interaction. In: Biochimica et Biophysica Acta - Molecular Cell Research. 2007 ; Vol. 1773, No. 12. pp. 1793-1800.
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