Protein-tyrosine phosphatase H1 controls growth hormone receptor signaling and systemic growth.
Journal:
J. Biol. Chem. 2007 NovAuthors:
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
Abstract
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 signif
...[more]icantly 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.[less]
Mesh Headings:
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