Related Experiment Video

Updated: Jul 11, 2026

Development and Application of Rapamycin-regulated Tyrosine Phosphatases
06:56

Development and Application of Rapamycin-regulated Tyrosine Phosphatases

Published on: September 6, 2024

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

Iwona Pilecka1, Claudia Patrignani, Rosanna Pescini

  • 1Merck Serono International, 1211 Geneva, Switzerland.

The Journal of Biological Chemistry
|October 9, 2007
PubMed

Insights

Protein-tyrosine phosphatases (PTPs) regulate growth hormone receptor (GHR) signaling. Mice lacking PTP-H1 showed enhanced growth, increased insulin-like growth factor 1, and improved bone density, revealing PTP-H1

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Endocrinology

Background:

  • Protein-tyrosine phosphatases (PTPs) are crucial regulators of cellular signaling pathways.
  • Growth hormone receptor (GHR) signaling controls somatic growth and metabolism.
  • The in vivo role of PTPs in GHR signaling and systemic growth remains largely unexplored.

Purpose of the Study:

  • To investigate the role of PTPs in modulating GHR signaling.
  • To identify specific PTPs that influence GHR signaling and systemic growth.
  • To elucidate the in vivo function of PTP-H1 in growth regulation.

Main Methods:

  • Screening of a PTP family-wide panel using molecular and cellular assays for GHR signaling interference.
  • In vivo studies utilizing knockout mice lacking the PTP-H1 catalytic domain.
  • Analysis of growth parameters, insulin-like growth factor 1 (IGF-1) expression, and bone characteristics.

Main Results:

  • PTP-H1 was identified as a key regulator of GHR signaling.
  • Mice deficient in PTP-H1 exhibited significantly enhanced growth compared to wild-type littermates.
  • PTP-H1 mutant mice displayed elevated plasma and liver IGF-1 mRNA expression, increased bone density, and higher mineral content.

Conclusions:

  • PTP-H1 plays a critical role in controlling systemic growth.
  • PTP-H1 modulates GHR signaling, influencing IGF-1 secretion and bone metabolism.
  • Targeting PTP-H1 may offer therapeutic strategies for growth modulation.

More Related Videos

Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development09:32

Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development

Published on: June 15, 2017

Assessing Cellular Target Engagement by SHP2 (PTPN11) Phosphatase Inhibitors08:45

Assessing Cellular Target Engagement by SHP2 (PTPN11) Phosphatase Inhibitors

Published on: July 17, 2020

Related Concept Videos

Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Receptor Tyrosine Kinases01:26

Receptor Tyrosine Kinases

Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...