Related Experiment Video

Updated: Feb 18, 2026

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

829

Jak2-mediated phosphorylation of Atoh1 is critical for medulloblastoma growth

Tiemo J Klisch1,2, Anna Vainshtein1,2, Akash J Patel1,3

  • 1Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, United States.

Elife
|November 24, 2017
PubMed

Insights

Reducing Atonal homologue 1 (Atoh1) levels or activity shows promise for treating pediatric Sonic Hedgehog medulloblastoma. Inhibiting Jak2-mediated phosphorylation of Atoh1 may offer a new therapeutic strategy for this aggressive brain tumor.

Area of Science:

  • Neuro-oncology
  • Molecular biology
  • Cancer genetics

Background:

  • Medulloblastoma is a common pediatric brain tumor with limited treatment options.
  • Sonic Hedgehog (Shh)-type medulloblastoma has a poor long-term survival rate.
  • The transcription factor Atonal homologue 1 (Atoh1) is crucial for Shh-type medulloblastoma development.

Purpose of the Study:

  • To investigate the therapeutic potential of reducing Atoh1 levels or activity in established Shh-type medulloblastoma.
  • To explore the role of Atoh1 modifications, specifically phosphorylation, in medulloblastoma growth.

Main Methods:

  • Studied the effect of Atoh1 heterozygosity on tumor development and survival in mice.
  • Investigated the phosphorylation of Atoh1 at tyrosine 78 mediated by Janus kinase 2 (Jak2).
  • Assessed the impact of Jak2 inhibition on Atoh1 phosphorylation and tumor growth in vivo.

Main Results:

  • Reducing Atoh1 levels (heterozygosity) decreased tumor occurrence and prolonged survival in a mouse model.
  • Atoh1 tyrosine 78 phosphorylation by Jak2 was identified in tumor-initiating cells and human Shh-medulloblastoma.
  • This phosphorylation stabilizes Atoh1 and enhances its transcriptional activity.
  • Jak2 inhibition effectively reduced Atoh1 phosphorylation and suppressed tumor growth in vivo.

Conclusions:

  • Targeting Atoh1 dosage or activity is a potential therapeutic strategy for Shh-type medulloblastoma.
  • Jak2-mediated phosphorylation of Atoh1 at tyrosine 78 is a critical oncogenic event in Shh-medulloblastoma.
  • Inhibiting this specific phosphorylation pathway presents a promising new therapeutic avenue for treating pediatric medulloblastoma.
Keywords:
Math1cancercancer biologydevelopmental biologyhumanmousestem cellstherapy

More Related Videos

Intracranial Orthotopic Allografting of Medulloblastoma Cells in Immunocompromised Mice05:10

Intracranial Orthotopic Allografting of Medulloblastoma Cells in Immunocompromised Mice

Published on: October 3, 2010

12.6K
A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors12:40

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors

Published on: December 7, 2014

15.3K

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...
4.9K
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...
5.7K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
7.4K
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...
13.2K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
8.7K
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
10.2K