The roles of specific residues on ERK2 for nuclear translocation in response to nerve growth factors in PC12 cells

Seunghee Yoon, Rony Seger, Eui Ju Choi, Young Sook Yoo

Research output: Contribution to journalArticle

Abstract

Extracellular signal-regulated kinases (ERKs) are phosphorylated on threonine and tyrosine residues at 183 and 185, respectively, and then translocated from cytosol to nucleus. ERK2 is retained in the nucleus for several hours by nerve growth factor (NGF), and this sustained retention of ERK2 in the nucleus has effect on the fate of biological response toward differentiation by neurite outgrowth in PC12 cells. The overexpression of Green Fluorescent Protein (GFP)-ERK2 and mutated GFP-ERK2 constructs without anchoring protein MEK1 were distributed throughout the resting and the activated cells. When GFP-ERK2 coexpressed along with MEK1, cytosolic localization of GFP-ERK2 is retained by MEK1 in the resting PC12 cells. This cytosolic retention was due to the binding of ERK2 to the MEK1. Upon stimulation by growth factors, the association between GFP-ERK2 and MEK1 was detached from each other, and then GFP-ERK2 was translocated into the nucleus. However, inactive form of the MKP-3 cytosolic phosphatase forced ERK cytosolic retention in PC12 cells were either left untreated or stimulated by NGF. When the transfected PC12 cells were treated for 72hrs with NGF, GFP-ERK2 was distributed the cytosol. Regarding its subcellular localization, the roles of residues 179-185 located in the activation loop of ERK2 were examined. The substitution of residues in the activation loop to alanine showed different localization on the nuclear translocation of ERK2 in PC12 cells.

Original languageEnglish
Pages (from-to)162-170
Number of pages9
JournalKey Engineering Materials
Volume277-279
Issue numberI
DOIs
Publication statusPublished - 2005

Keywords

  • GFP-ERK2
  • MEK1
  • MKP-3
  • Nerve growth factor
  • Nuclear translocation
  • PC12 cells

ASJC Scopus subject areas

  • Materials Science(all)
  • Mechanics of Materials
  • Mechanical Engineering

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