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Open AccessArticle

Characterization of Integrin αIIbβ3-Mediated Outside-in Signaling by Protein Kinase Cδ in Platelets

1
College of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Korea
2
College of Veterinary Medicine and Veterinary Medical Research Institute, Jeju National University, Jeju 63243, Korea
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(18), 6563; https://doi.org/10.3390/ijms21186563
Received: 10 August 2020 / Revised: 1 September 2020 / Accepted: 7 September 2020 / Published: 8 September 2020
(This article belongs to the Special Issue Physiology of Platelets in Humans and Animals)
Engagement of integrin αIIbβ3 promotes platelet–platelet interaction and stimulates outside-in signaling that amplifies activation. Protein kinase Cδ (PKCδ) is known to play an important role in platelet activation, but its role in outside-in signaling has not been established. In the present study, we determined the role of PKCδ and its signaling pathways in integrin αIIbβ3-mediated outside-in signaling in platelets using PKCδ-deficient platelets. Platelet spreading to immobilized fibrinogen resulted in PKCδ phosphorylation, suggesting that αIIbβ3 activation caused PKCδ activation. αIIbβ3-mediated phosphorylation of Akt was significantly inhibited in PKCδ -/- platelets, indicating a role of PKCδ in outside-in signaling. αIIbβ3-mediated PKCδ phosphorylation was inhibited by proline-rich tyrosine kinase 2 (Pyk2) selective inhibitor, suggesting that Pyk2 contributes to the regulation of PKCδ phosphorylation in outside-in signaling. Additionally, Src-family kinase inhibitor PP2 inhibited integrin-mediated Pyk2 and PKCδ phosphorylation. Lastly, platelet spreading was inhibited in PKCδ -/- platelets compared to the wild-type (WT) platelets, and clot retraction from PKCδ -/- platelets was markedly delayed, indicating that PKCδ is involved in the regulation of αIIbβ3-dependent interactivities with cytoskeleton elements. Together, these results provide evidence that PKCδ plays an important role in outside-in signaling, which is regulated by Pyk2 in platelets. View Full-Text
Keywords: PKCδ; Pyk2; αIIbβ3; spreading; platelets PKCδ; Pyk2; αIIbβ3; spreading; platelets
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MDPI and ACS Style

Chaudhary, P.K.; Kim, S.; Jee, Y.; Lee, S.-H.; Kim, S. Characterization of Integrin αIIbβ3-Mediated Outside-in Signaling by Protein Kinase Cδ in Platelets. Int. J. Mol. Sci. 2020, 21, 6563. https://doi.org/10.3390/ijms21186563

AMA Style

Chaudhary PK, Kim S, Jee Y, Lee S-H, Kim S. Characterization of Integrin αIIbβ3-Mediated Outside-in Signaling by Protein Kinase Cδ in Platelets. International Journal of Molecular Sciences. 2020; 21(18):6563. https://doi.org/10.3390/ijms21186563

Chicago/Turabian Style

Chaudhary, Preeti K.; Kim, Sanggu; Jee, Youngheun; Lee, Seung-Hun; Kim, Soochong. 2020. "Characterization of Integrin αIIbβ3-Mediated Outside-in Signaling by Protein Kinase Cδ in Platelets" Int. J. Mol. Sci. 21, no. 18: 6563. https://doi.org/10.3390/ijms21186563

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