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The regulation of Sema4D exodomain shedding by protein kinase A in platelets

T Chen1, D Z Xu1, Q Li1

  • 1a Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, MOH Key Lab of Thrombosis and Hemostasis, Jiangsu Institute of Hematology, Jiangsu Key Lab of Preventive and Translational Medicine for Geriatric Diseases, Soochow University , Suzhou , China.

Platelets
|November 5, 2016
PubMed

Insights

Protein kinase A (PKA) regulates Sema4D shedding from platelets. PKA inhibition promotes shedding via ADAM17, while PKA activation inhibits it, revealing a novel regulatory pathway.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Hematology

Background:

  • Sema4D is expressed on platelet plasma membranes and can be cleaved by ADAM17.
  • This shedding produces biologically active exodomain fragments and membrane-associated remnant fragments.
  • Calmodulin modulates this cleavage process.

Purpose of the Study:

  • To investigate the role of protein kinase A (PKA) in Sema4D shedding from platelets.
  • To elucidate the regulatory mechanisms of Sema4D shedding.

Main Methods:

  • Pharmacological inhibition and activation of PKA using H89.
  • Analysis of Sema4D shedding and its association with ADAM17 and calmodulin.
  • Identification of cleavage sites within the juxtamembrane region.

Main Results:

  • PKA inhibition with H89 induced Sema4D exodomain shedding.
  • PKA activation inhibited agonist-initiated Sema4D shedding.
  • Shedding induced by PKA inhibition is ADAM17-mediated and does not involve calmodulin dissociation.

Conclusions:

  • PKA plays a significant role in regulating Sema4D shedding in platelets.
  • PKA inhibition represents a novel mechanism for inducing Sema4D shedding.
  • ADAM17 mediates variable cleavages in the juxtamembrane region during Sema4D shedding.
Keywords:
PKAPlateletsSema4D

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