Related Experiment Video

Updated: May 18, 2026

Study of the Functions and Activities of Neuronal K-Cl Co-Transporter KCC2 Using Western Blotting
10:08

Study of the Functions and Activities of Neuronal K-Cl Co-Transporter KCC2 Using Western Blotting

Published on: December 9, 2022

NOK/STYK1 interacts with GSK-3β and mediates Ser9 phosphorylation through activated Akt

Jing Li1, Fang Wu, Feng Sheng

  • 1State Key Laboratory of Biomembranes and Membrane Biotechnology, School of Life Sciences, Tsinghua University, Beijing 100084, China.

FEBS Letters
|September 27, 2012
PubMed

Insights

NOK, a known oncogene, regulates breast cancer progression by forming a complex with Akt and GSK-3β. This interaction enhances GSK-3β phosphorylation, potentially driving tumor development.

Area of Science:

  • Molecular Biology
  • Oncology
  • Cell Signaling

Background:

  • The oncogenic role of NOK (STYK1) is established, but its precise molecular functions remain unclear.
  • Understanding NOK's regulatory mechanisms is crucial for deciphering its contribution to tumorigenesis.

Purpose of the Study:

  • To elucidate the biochemical and biological activities of NOK as a molecular regulator.
  • To identify novel signaling pathways and protein interactions involving NOK.

Main Methods:

  • Investigated the effect of NOK overexpression on the phosphorylation status of GSK-3β and Akt.
  • Utilized co-immunoprecipitation assays to determine complex formation between NOK, Akt, and GSK-3β.
  • Correlated the expression levels of NOK, phosphorylated Akt (p-Akt), and phosphorylated GSK-3β (p-GSK-3β) in breast cell lines.

Main Results:

  • Overexpression of NOK enhanced GSK-3β phosphorylation at Ser9, mediated by Akt phosphorylation at Thr308.
  • NOK was found to form molecular complexes with both Akt and GSK-3β.
  • Positive correlations were observed between NOK, p-Akt(Thr308), and p-GSK-3β(Ser9) expression in various breast cell lines.

Conclusions:

  • Identified a novel functional molecular complex comprising NOK, Akt, and GSK-3β.
  • This NOK-Akt-GSK-3β complex may mediate a NOK-driven tumorigenic cascade in breast cancer.
  • NOK acts as a key regulator in a signaling pathway influencing GSK-3β activity.

More Related Videos

Oligopeptide Competition Assay for Phosphorylation Site Determination09:16

Oligopeptide Competition Assay for Phosphorylation Site Determination

Published on: May 18, 2017

Related Concept Videos

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...
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...
Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...