Related Experiment Video

Updated: Aug 15, 2026

Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome
07:23

Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome

Published on: June 15, 2016

JAK-STAT signaling activated by Abl oncogenes

N N Danial1, P Rothman

  • 1Department of Microbiology, Integrated Program in Molecular, Cellular and Biophysical Studies, College of Physicians and Surgeons of Columbia University, 630 168th Street West, New York, NY 10032, USA.

Oncogene
|June 13, 2000
PubMed

Insights

The v-Abl oncoprotein requires Janus kinases (JAKs) for STAT activation and cellular transformation. Direct interaction between v-Abl and JAKs is crucial for these oncogenic functions.

Area of Science:

  • Molecular Oncology
  • Signal Transduction

Background:

  • Abl oncoproteins, including v-Abl and BCR-Abl, activate Signal Transducers and Activators of Transcription (STAT) proteins.
  • The precise mechanisms of STAT activation by these oncoproteins are not fully elucidated.

Purpose of the Study:

  • To investigate the role of Janus kinases (JAKs) in v-Abl-mediated STAT activation and cellular transformation.
  • To identify the interaction domain between v-Abl and JAK kinases.

Main Methods:

  • Physical association studies between v-Abl and JAK kinases.
  • Mutagenesis of v-Abl to map the JAK interaction domain.
  • Assessment of JAK kinase activity and its impact on v-Abl-induced cellular proliferation and transformation.
  • Analysis of downstream signaling pathways including Akt, PI3-kinase, STATs, and Ras.

Main Results:

  • Constitutive activation of JAK tyrosine kinases was observed in v-Abl-transformed cells.
  • v-Abl directly interacts with JAK kinases via its carboxyl-terminal region.
  • A v-Abl mutant lacking the JAK interaction domain failed to activate STATs, induce proliferation, and transform cells.
  • Inhibition of JAK 1 kinase activity impaired v-Abl's ability to activate STATs, induce proliferation, and transform bone marrow cells.
  • Defects in v-Abl-mediated activation of Akt, PI3-kinase, STATs, and Ras pathways were observed when JAK activity was inhibited.

Conclusions:

  • JAK kinases play a critical role in v-Abl-induced cellular transformation.
  • Direct interaction between v-Abl and JAKs is essential for STAT activation and oncogenesis.
  • JAKs mediate the activation of multiple signaling pathways crucial for v-Abl's oncogenic functions.

More Related Videos

Merging Absolute and Relative Quantitative PCR Data to Quantify STAT3 Splice Variant Transcripts11:19

Merging Absolute and Relative Quantitative PCR Data to Quantify STAT3 Splice Variant Transcripts

Published on: October 9, 2016

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
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...
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...
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...
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...
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...