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Protein-tyrosine phosphatase H1 controls growth hormone receptor signaling and systemic growth.

Several protein-tyrosine phosphatases (PTPs) have been implicated in the control of growth hormone receptor (GHR) signaling, but none have been shown to affect growth in vivo. We have applied a battery of molecular and cellular approaches to test a family-wide panel of PTPs for interference with GHR signaling. Among the subset of PTPs that showed activity in multiple readouts, we selected PTP-H1/PTPN3 for further in vivo studies and found that mice lacking the PTP-H1 catalytic domain show significantly enhanced growth over their wild type littermates. In addition, PTP-H1 mutant animals had enhanced plasma and liver mRNA expression of insulin-like growth factor 1, as well as increased bone density and mineral content. These observations point to a controlling role for PTP-H1 in modulating GHR signaling and systemic growth through insulin-like growth factor 1 secretion.

Pubmed ID: 17921143

Authors

  • Pilecka I
  • Patrignani C
  • Pescini R
  • Curchod ML
  • Perrin D
  • Xue Y
  • Yasenchak J
  • Clark A
  • Magnone MC
  • Zaratin P
  • Valenzuela D
  • Rommel C
  • Hooft van Huijsduijnen R

Journal

The Journal of biological chemistry

Publication Data

November 30, 2007

Associated Grants

None

Mesh Terms

  • Animals
  • Catalytic Domain
  • Cell Proliferation
  • Female
  • Humans
  • Insulin-Like Growth Factor I
  • Liver
  • Male
  • Mice
  • Mice, Knockout
  • Models, Biological
  • Mutation
  • Phosphorylation
  • Protein Tyrosine Phosphatase, Non-Receptor Type 3
  • RNA, Messenger
  • Receptors, Somatotropin
  • Signal Transduction