Research Articles

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



Background: Spatio-temporal control of extracellular signal-regulated kinase (ERK) activity, a critical determinant of the cell's response to growth factors, requires timely dephosphorylation of its regulatory tyrosine and/or threonine residue by MAPK phosphatases. We studied the physiological role of kinase interaction motif (KIM)-containing protein tyrosine phosphatases (PTPs) in the control of EGF- and NGF-induced ERK activity in neuroendocrine PC12 cells.

Results: We found a single KIM-containing PTP to be endogenously expressed in rat PC12 cells: the transmembrane PTPRR isoform termed PCPTP1. Protein knock-down of PCPTP1, or fourfold overexpression of its mouse orthologue, PTPBR7, left EGF- and NGF-induced ERK1/2 activity in PC12 cells unaltered. Ectopic expression of cytosolic PTPRR isoforms, however, resulted in reduced EGF-induced ERK1/2 activity, an effect that was dependent on the phosphatase activity and the KIM-domain of these PTPs.

Conclusion: The finding that robust changes in tyrosine-specific MAPK phosphatase expression levels have minor effects on temporal ERK1/2 activity control in PC12 cells suggests that dualspecificity MAPK phosphatases may act as major regulators of growth factor-induced ERK1/2 signaling in these cells.

  • Year: 2006
  • Volume: 1
  • Page/Article: Art. 4
  • DOI: 10.1186/1750-2187-1-4
  • Submitted on 4 Sep 2006
  • Accepted on 29 Nov 2006
  • Published on 29 Nov 2006