Related Experiment Video

Updated: May 22, 2026

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
12:26

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay

Published on: May 3, 2018

Regulation of p27 (Kip1) by mitogen-induced tyrosine phosphorylation

Heidelinde Jäkel1, Ines Peschel, Clarissa Kunze

  • 1Division of Medical Biochemistry; Biocenter; Innsbruck Medical University; Innsbruck, Austria.

Cell Cycle (Georgetown, Tex.)
|May 15, 2012
PubMed

Insights

Janus kinase 2 (JAK2) phosphorylates the p27 protein, impairing its function and promoting degradation. This links growth factor signaling to cell cycle regulation, with oncogenes exploiting this pathway.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Cancer Biology

Background:

  • Extracellular signals initiate mitogen-activated protein kinase (MAPK) pathways via receptor binding.
  • Tyrosine kinases, including Src, Lyn, and JAK2, play critical roles in signal transduction.
  • The cyclin-dependent kinase (Cdk) inhibitor p27 (Kip1) regulates cell cycle progression.

Purpose of the Study:

  • To investigate the role of Janus kinase 2 (JAK2) in the regulation of p27 (Kip1).
  • To elucidate the mechanism by which JAK2 affects p27 (Kip1) activity and stability.
  • To understand how JAK2 links growth factor signaling to cell cycle control.

Main Methods:

  • Investigated the interaction between JAK2 and p27 (Kip1).
  • Utilized biochemical assays to confirm JAK2-mediated phosphorylation of p27 (Kip1) at tyrosine residue 88 (Y88).
  • Assessed the impact of JAK2 phosphorylation on p27 (Kip1) inhibitory activity and proteasomal degradation.

Main Results:

  • JAK2 directly binds and phosphorylates p27 (Kip1) at Y88.
  • Phosphorylation by JAK2 impairs p27 (Kip1)'s ability to inhibit Cdks.
  • JAK2-mediated phosphorylation promotes ubiquitin-dependent degradation of p27 (Kip1).

Conclusions:

  • JAK2 acts as a crucial link between cytokine/growth factor signaling and p27 (Kip1) regulation.
  • Aberrant activation of JAK2, as seen in oncogenic mutations (e.g., JAK2V617F), can lead to p27 (Kip1) inactivation.
  • This pathway provides a mechanism for oncogenes to promote cell proliferation by downregulating Cdk inhibitors.

More Related Videos

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols12:02

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols

Published on: June 6, 2017

Combining Mitotic Cell Synchronization and High Resolution Confocal Microscopy to Study the Role of Multifunctional Cell Cycle Proteins During Mitosis08:33

Combining Mitotic Cell Synchronization and High Resolution Confocal Microscopy to Study the Role of Multifunctional Cell Cycle Proteins During Mitosis

Published on: December 5, 2017

Related Concept Videos

Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Inhibition of CDK Activity02:34

Inhibition of CDK Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
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...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
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...