Syndecan-4 regulates platelet-derived growth factor-mediated MAP kinase activation by altering intracellular reactive

Jungyean Kim1, Jung-hyun Lee, Hey Sun Park

  • 1Department of Life Sciences, Division of Life and Pharmaceutical Sciences and the Center for Cell Signaling and Drug Discovery Research, Ewha Womans University, Daehyun-dong, Seodaemoon-Gu, Seoul 120-750, Republic of Korea.

FEBS Letters
|July 16, 2008
PubMed

Insights

Syndecan-4 increases reactive oxygen species (ROS) by regulating the NADH oxidase component Nox1. This mechanism mediates platelet-derived growth factor-induced MAP kinase activation in cells.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Molecular Biology

Background:

  • Syndecan-4 is a cell adhesion receptor involved in cellular interactions.
  • Cell adhesion is increasingly linked to the generation of reactive oxygen species (ROS).

Purpose of the Study:

  • To investigate the role of syndecan-4 in regulating growth factor-induced ROS generation.
  • To understand the molecular mechanisms by which syndecan-4 influences ROS production and downstream signaling.

Main Methods:

  • Overexpression of syndecan-4 in rat embryo fibroblasts (REFs).
  • Knockdown of Nox1 expression using small inhibitory RNAs.
  • Measurement of ROS levels.
  • Assessment of MAP kinase activity.

Main Results:

  • Syndecan-4 overexpression led to increased ROS levels in REFs.
  • Nox1 expression was upregulated in syndecan-4-overexpressing cells.
  • Knockdown of Nox1 diminished syndecan-4-mediated ROS generation.
  • Syndecan-4 enhanced platelet-derived growth factor (PDGF)-induced MAP kinase activity, correlating with ROS generation.

Conclusions:

  • Syndecan-4 plays a key role in regulating ROS generation.
  • Syndecan-4-mediated ROS production involves the NADH oxidase component Nox1.
  • Syndecan-4 regulates PDGF-induced MAP kinase activation through modulation of ROS generation.

Related Concept Videos

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...
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...
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
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...
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...