2. Academic Validation
  3. Platelet integrin αIIbβ3: signal transduction, regulation, and its therapeutic targeting

Platelet integrin αIIbβ3: signal transduction, regulation, and its therapeutic targeting

  • J Hematol Oncol. 2019 Mar 7;12(1):26. doi: 10.1186/s13045-019-0709-6.
Jiansong Huang 1 2 3,  Xia Li 1 2 3,  Xiaofeng Shi 4,  Mark Zhu 1,  Jinghan Wang 1 2 3,  Shujuan Huang 1 2 3,  Xin Huang 1 2 3,  Huafeng Wang 1 2 3 5,  Ling Li 5,  Huan Deng 6,  Yulan Zhou 7,  Jianhua Mao 8 9,  Zhangbiao Long 10,  Zhixin Ma 11,  Wenle Ye 1 2 3,  Jiajia Pan 1 2 3,  Xiaodong Xi 12 13,  Jie Jin 14 15 16
Affiliations

Affiliations

  • 1 Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
  • 2 Key Laboratory of Hematologic Malignancies, Diagnosis and Treatment, Hangzhou, Zhejiang, China.
  • 3 Institute of Hematology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
  • 4 Department of Hematology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China.
  • 5 Department of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, Hematologic Malignancies and Stem Cell Transplantation Institute, Beckman Research Institute, City of Hope Medical Center, Duarte, CA, 91010, USA.
  • 6 Department of Pathology, The Fourth Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
  • 7 Department of Hematology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
  • 8 State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Collaborative Innovation Center of Hematology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 9 Sino-French Research Centre for Life Sciences and Genomics, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 10 Department of Hematology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
  • 11 Clinical Prenatal Diagnosis Center, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
  • 12 State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Collaborative Innovation Center of Hematology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. [email protected].
  • 13 Sino-French Research Centre for Life Sciences and Genomics, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. [email protected].
  • 14 Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. [email protected].
  • 15 Key Laboratory of Hematologic Malignancies, Diagnosis and Treatment, Hangzhou, Zhejiang, China. [email protected].
  • 16 Institute of Hematology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. [email protected].
PMID: 30845955 DOI: 10.1186/s13045-019-0709-6
Abstract

Integrins are a family of Transmembrane Glycoprotein signaling receptors that can transmit bioinformation bidirectionally across the plasma membrane. Integrin αIIbβ3 is expressed at a high level in platelets and their progenitors, where it plays a central role in platelet functions, hemostasis, and arterial thrombosis. Integrin αIIbβ3 also participates in Cancer progression, such as tumor cell proliferation and metastasis. In resting platelets, Integrin αIIbβ3 adopts an inactive conformation. Upon agonist stimulation, the transduction of inside-out signals leads Integrin αIIbβ3 to switch from a low- to high-affinity state for fibrinogen and Other ligands. Ligand binding causes Integrin clustering and subsequently promotes outside-in signaling, which initiates and amplifies a range of cellular events to drive essential platelet functions such as spreading, aggregation, clot retraction, and thrombus consolidation. Regulation of the bidirectional signaling of Integrin αIIbβ3 requires the involvement of numerous interacting proteins, which associate with the cytoplasmic tails of αIIbβ3 in particular. Integrin αIIbβ3 and its signaling pathways are considered promising targets for antithrombotic therapy. This review describes the bidirectional signal transduction of Integrin αIIbβ3 in platelets, as well as the proteins responsible for its regulation and therapeutic agents that target Integrin αIIbβ3 and its signaling pathways.

Keywords

Integrin αIIbβ3; Kindlin; Signal transduction; Talin; Therapeutic targeting; Transmembrane proteins.

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