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Tyrosine-specific MAPK phosphatases and the control of ERK signaling in PC12 cells

Yvet E Noordman1, Patrick A M Jansen, Wiljan J A J Hendriks

  • 1Department of Cell Biology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Geert Grooteplein 28, 6525 GA Nijmegen, The Netherlands. y.noordman@ncmls.ru.nl

Journal of Molecular Signaling
|January 17, 2007
PubMed
Abstract

Insights

Kinase interaction motif (KIM)-containing protein tyrosine phosphatases (PTPs) minimally impact ERK activity in PC12 cells. Dual-specificity MAPK phosphatases are likely key regulators of growth factor signaling.

Area of Science:

  • Cellular signaling
  • Molecular biology
  • Signal transduction

Background:

  • Extracellular signal-regulated kinase (ERK) activity is crucial for cellular responses to growth factors.
  • MAPK phosphatases regulate ERK activity through dephosphorylation.
  • The role of KIM-containing PTPs in ERK regulation was investigated.

Purpose of the Study:

  • To determine the physiological role of KIM-containing PTPs in controlling ERK activity.
  • To investigate the impact of PTPRR isoforms on EGF- and NGF-induced ERK activity in PC12 cells.

Main Methods:

  • Studied endogenous and overexpressed PTPRR isoforms in rat PC12 cells.
  • Utilized protein knock-down and overexpression techniques.
  • Assessed EGF- and NGF-induced ERK1/2 activity.

Main Results:

  • Identified PCPTP1 (transmembrane PTPRR) as the sole endogenous KIM-containing PTP in PC12 cells.
  • Knock-down or overexpression of PCPTP1/PTPBR7 did not alter EGF/NGF-induced ERK1/2 activity.
  • Ectopic expression of cytosolic PTPRR isoforms reduced EGF-induced ERK1/2 activity in a phosphatase- and KIM-dependent manner.

Conclusions:

  • Tyrosine-specific MAPK phosphatases have a limited role in temporal ERK1/2 activity control.
  • Dual-specificity MAPK phosphatases are likely the primary regulators of growth factor-induced ERK1/2 signaling in PC12 cells.

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