Related Experiment Video

Updated: Jul 17, 2026

Assessing Cellular Target Engagement by SHP2 (PTPN11) Phosphatase Inhibitors
08:45

Assessing Cellular Target Engagement by SHP2 (PTPN11) Phosphatase Inhibitors

Published on: July 17, 2020

SHP-2 regulates cell growth by controlling the mTOR/S6 kinase 1 pathway

Christina I Zito1, Hui Qin, John Blenis

  • 1Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.

The Journal of Biological Chemistry
|January 19, 2007
PubMed

Insights

SHP-2 protein suppresses cell growth by inhibiting S6K1 activity, particularly during low energy states. This regulation occurs through the energy-sensing AMPK pathway, revealing SHP-2

Area of Science:

  • Cellular Biology
  • Molecular Signaling
  • Biochemistry

Background:

  • Cell growth relies on macromolecular biosynthesis, with S6 ribosomal kinase 1 (S6K1) being crucial.
  • The upstream regulators of S6K1 signaling, especially during early events, are not fully understood.
  • Growth factor deprivation impacts cellular energy levels, influencing signaling pathways.

Purpose of the Study:

  • To investigate the role of SHP-2 in regulating S6K1 activity.
  • To elucidate the mechanism by which SHP-2 influences cell growth under nutrient-limited conditions.
  • To determine if the energy-sensing AMPK pathway is involved in SHP-2-mediated S6K1 regulation.

Main Methods:

  • Utilized fibroblasts lacking functional SHP-2 and small interfering RNA (siRNA) for SHP-2 knockdown.
  • Assessed S6K1 activity in cells under growth factor deprivation.
  • Measured cell size in SHP-2 deficient versus wild-type cells.
  • Investigated the effect of SHP-2 on AMPK activity under low energy conditions.

Main Results:

  • SHP-2 deficiency led to increased S6K1 activity and cell size during growth factor deprivation.
  • SHP-2 was found to promote AMPK activity in low energy states.
  • These findings suggest SHP-2 acts upstream of AMPK to regulate S6K1.

Conclusions:

  • SHP-2 acts as an early suppressor of S6K1 signaling.
  • SHP-2 negatively regulates S6K1 through an AMPK-dependent pathway.
  • SHP-2 plays a critical role in limiting cell growth under low energy conditions.

More Related Videos

Development and Application of Rapamycin-regulated Tyrosine Phosphatases06:56

Development and Application of Rapamycin-regulated Tyrosine Phosphatases

Published on: September 6, 2024

Quantitative PCR-based Assay to Measure Sonic Hedgehog Signaling in Cellular Model of Ciliogenesis07:26

Quantitative PCR-based Assay to Measure Sonic Hedgehog Signaling in Cellular Model of Ciliogenesis

Published on: January 31, 2025

Related Concept Videos

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...
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...
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...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...