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.
Pilecka
Iwona
I
Merck Serono International, 1211 Geneva, Switzerland.
Patrignani
Claudia
C
Pescini
Rosanna
R
Curchod
Marie-Laure
ML
Perrin
Dominique
D
Xue
Yingzi
Y
Yasenchak
Jason
J
Clark
Ann
A
Magnone
Maria Chiara
MC
Zaratin
Paola
P
Valenzuela
David
D
Rommel
Christian
C
Hooft van Huijsduijnen
Rob
R
D000818:Animals; D020134:Catalytic Domain; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D009154:Mutation; D010766:Phosphorylation; D054589:Protein Tyrosine Phosphatase, Non-Receptor Type 3 / Q000737:chemistry* / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D011986:Receptors, Somatotropin / Q000378:metabolism*; D015398:Signal Transduction
D012333:RNA, Messenger; D011986:Receptors, Somatotropin; D007334:Insulin-Like Growth Factor I; D054589:Protein Tyrosine Phosphatase, Non-Receptor Type 3