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Extracellular signal-regulated kinase 5 associates with casein kinase II to regulate GPIb-IX-mediated platelet

Z Cheng1, W Gao2, X Fan3

  • 1Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Journal of Thrombosis and Haemostasis : JTH
|June 13, 2017
PubMed

Insights

Extracellular signal-regulated kinase 5 (ERK5) and casein kinase II (CKII) interact in human platelets. This association regulates PI3K/Akt pathway activation, crucial for GPIb-IX signaling and platelet activation.

Area of Science:

  • Platelet biology
  • Molecular signaling
  • Signal transduction pathways

Background:

  • The platelet glycoprotein (GP) Ib-IX complex is vital for thrombosis and hemostasis.
  • While ERK1/2 and p38 MAPKs are known players in GPIb-IX signaling, ERK5's role remains uncharacterized.

Purpose of the Study:

  • To elucidate the function and underlying mechanisms of extracellular signal-regulated kinase 5 (ERK5) in GPIb-IX-mediated platelet activation.

Main Methods:

  • Assessed ERK5 function in human platelets using botrocetin/VWF and ristocetin/VWF stimulation, and VWF shear stress adhesion assays.
  • Identified ERK5-interacting proteins via mass spectrometry in CHO cells and confirmed in human platelets.
  • Utilized specific inhibitors for ERK5 and identified interacting proteins to clarify pathway roles.

Main Results:

  • ERK5 phosphorylation increased upon GPIb-IX complex stimulation.
  • ERK5 inhibition suppressed platelet aggregation and adhesion.
  • Casein kinase II (CKII) was identified as an ERK5-binding protein, and CKII inhibition mimicked ERK5 inhibition effects on PTEN/PI3K/Akt signaling.

Conclusions:

  • ERK5 associates with CKII to regulate GPIb-IX-mediated platelet activation.
  • The PTEN/PI3K/Akt pathway is a key downstream mediator of this ERK5-CKII interaction.
Keywords:
PTENcasein kinase IIextracellular signal-regulated kinase 5platelet activationplatelet glycoprotein GPIb-IX complex

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