Frontiers of Medicine

, Volume 10, Issue 3, pp 311–319 | Cite as

Roles of integrin β3 cytoplasmic tail in bidirectional signal transduction in a trans-dominant inhibition model

  • Jiansong Huang
  • Yulan Zhou
  • Xiaoyu Su
  • Yuanjing Lyu
  • Lanlan Tao
  • Xiaofeng Shi
  • Ping Liu
  • Zhangbiao Long
  • Zheng Ruan
  • Bing Xiao
  • Wenda Xi
  • Quansheng Zhou
  • Jianhua MaoEmail author
  • Xiaodong XiEmail author
Research Article


We evaluated the roles of calpain cleavage-related mutations of the integrin β3 cytoplasmic tail in integrin αIIbβ3 bidirectional signaling using a trans-dominant inhibition model. Chimeric Tac-β3 proteins (i.e., Tac-β3, Tac-β3Δ741, Tac-β3Δ747, Tac-β3Δ754, Tac-β3Δ759, and Tac-β3ΔNITY) consisting of the extracellular and transmembrane domains of human IL-2 receptor (Tac) and the human integrin β3 cytoplasmic domain were stably expressed in the 123 CHO cells harboring human glycoprotein Ib-IX and wild-type integrin αIIbβ3. The different cells were assayed for stable adhesion and spreading on immobilized fibrinogen, and for binding soluble fibrinogen representing outside-in and inside-out signaling events, respectively. The chimeric protein Tac-β3 inhibited, and Tac-β3ΔNITY partially attenuated stable adhesion and spreading. Tac-β3, Tac-β3Δ759, Tac-β3ΔNITY, and Tac-β3Δ754, but not Tac-β3Δ747 or Tac-β3Δ741, impaired the soluble fibrinogen binding. Results indicated that the bidirectional signaling was significantly inhibited by Tac-β3 and Tac-β3ΔNITY, albeit to a much lesser extent. Moreover, only inside-out signaling was impaired in the 123/Tac-β3Δ759 and 123/Tac-β3Δ754 cells in contrast to an intact bidirectional signaling in the 123/Tac-β3Δ747 and 123/Tac-β3Δ741 cells. In conclusion, the calpain cleavage of integrin β3 resulted in the regulatory effects on signaling by interrupting its interaction with cytoplasmic proteins rather than altering its conformation, and may thus regulate platelet function.


integrin β3 signal transduction trans-dominant inhibition model 


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Copyright information

© Higher Education Press and Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Jiansong Huang
    • 1
    • 2
  • Yulan Zhou
    • 1
    • 3
  • Xiaoyu Su
    • 1
  • Yuanjing Lyu
    • 1
  • Lanlan Tao
    • 1
  • Xiaofeng Shi
    • 1
    • 4
  • Ping Liu
    • 1
    • 5
  • Zhangbiao Long
    • 1
    • 6
  • Zheng Ruan
    • 1
  • Bing Xiao
    • 1
  • Wenda Xi
    • 7
  • Quansheng Zhou
    • 8
  • Jianhua Mao
    • 1
    Email author
  • Xiaodong Xi
    • 1
    • 9
    Email author
  1. 1.State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Collaborative Innovation Center of HematologyRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina
  2. 2.Institute of Hematology, The First Affiliated Hospital, School of MedicineZhejiang UniversityHangzhouChina
  3. 3.Department of HematologyThe First Affiliated Hospital of Nanchang UniversityNanchangChina
  4. 4.Department of HematologyAffiliated Hospital of Jiangsu UniversityZhenjiangChina
  5. 5.Department of Pediatrics, Renji HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
  6. 6.Department of Hematology, Peking Union Medical College HospitalChinese Academy of Medical Sciences & Peking Union Medical CollegeBeijingChina
  7. 7.Shanghai Institute of HypertensionRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina
  8. 8.Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, 2011 Collaborative Innovation Center of HematologySoochow UniversitySuzhouChina
  9. 9.Sino-French Research Centre for Life Sciences and GenomicsRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina

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