NOK/STYK1 has a strong tendency towards forming aggregates and colocalises with epidermal growth factor receptor in

Xue Ding1, Qing-Bo Jiang, Rui Li

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

Insights

Novel Oncogene with Kinase-domain (NOK) aggregates in early endosomes and colocalizes with the epidermal growth factor receptor (EGFR). NOK facilitates EGFR trafficking, suggesting a role in post-internalization signaling.

Area of Science:

  • Cell Biology
  • Molecular Oncology
  • Signal Transduction

Background:

  • The Novel Oncogene with Kinase-domain (NOK)/STYK1 is implicated in cellular transformation, tumorigenesis, and metastasis.
  • Understanding the subcellular localization and function of NOK is crucial for cancer research.

Purpose of the Study:

  • To characterize the subcellular distribution of NOK in HeLa cells.
  • To investigate the interaction of NOK with the epidermal growth factor receptor (EGFR).
  • To elucidate the role of NOK in EGFR trafficking and signaling.

Main Methods:

  • Confocal immunolocalization studies in HeLa cells.
  • Immunohistochemistry (IHC) analysis of pathological tissues.
  • Co-localization studies with EGFR and EGF stimulation.

Main Results:

  • NOK exhibits distinct structural subtypes and expression patterns (dot and aggregation patterns).
  • Endogenous NOK forms aggregate-like structures in vivo.
  • NOK localizes to early endosomes and co-localizes with EGFR in activated endosomal vesicles.
  • NOK facilitates EGFR trafficking from early endosomes to later endosomes/lysosomes, while NOK levels remain stable.
  • NOK demonstrates a propensity for aggregate formation.

Conclusions:

  • NOK's subcellular localization and aggregation tendency have significant physiological implications.
  • This study provides the first evidence of NOK co-localization with EGFR in endosomes.
  • NOK participates in the post-internalization steps of EGFR signaling, potentially influencing cancer progression.

Related Concept Videos

Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
Anchoring Junctions01:03

Anchoring Junctions

Anchoring junctions are multiprotein complexes that help cells connect to other cells and the extracellular matrix. Anchoring junctions are present on the lateral and basal surfaces of cells, providing strong and flexible connections. Focal adhesions are often formed due to cell interactions with the ECM substrata, which initiate signal transduction via kinase cascades and other mechanisms. Together, they provide stability and tissue integrity. There are three types of anchoring junctions:...
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...
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Vesicular Tubular Clusters01:45

Vesicular Tubular Clusters

After budding out from the ER membrane, some COPII vesicles lose their coat and fuse with one another to form larger vesicles and interconnected tubules called vesicular tubular clusters or VTCs. These clusters constitute a compartment at the ER-Golgi interface known as ERGIC (Endoplasmic Reticulum Golgi Intermediate Compartment). The ERGIC is a mobile membrane-bound cargo transport system that sorts proteins secreted from ER and delivers them to the Golgi.
With the help of motor proteins such...
Enzyme-linked Receptors01:00

Enzyme-linked Receptors

Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...