Disabled-2 is a novel αIIb-integrin-binding protein that negatively regulates platelet-fibrinogen interactions and platelet aggregation

Chien-Ling Huang, Ju Chien Cheng, Arnold Stern, Jer Tsong Hsieh, Chang Hui Liao, Ching Ping Tseng

Research output: Journal article publicationJournal articleAcademic researchpeer-review

30 Citations (Scopus)


Platelet aggregation plays a pivotal role in the haemostatic process and is involved in the pathological counterpart of arterial thrombosis. We have shown that the adapter protein disabled-2 (DAB2) is expressed abundantly in platelets. In this study, DAB2 was found to distribute in the platelet α-granules and was released from the granular compartment upon platelet activation. The secreted DAB2 binds to the extracellular region of αIIbβ3 integrin on the platelet surface through the phosphotyrosine-binding domain. The DAB2-platelet interactions result in the inhibition of agonist-induced platelet aggregation with the exception of thrombin, a DAB2 protease that renders DAB2 inactive. Biochemical and mutational analysis revealed that the DAB2 cell-adhesion Arg-Gly-Asp (RGD) motif (amino acid residues 64-66) and the αIIb-integrin-fibrinogen-binding region (amino acid residues 171-464) are important for the binding of αIIb integrin with fibrinogen and provide a mechanism for DAB2 to inhibit platelet aggregation. Accordingly, the synthetic RGD-motif-containing DAB2 peptide PDARGDKM also elicited anti-platelet aggregation activity. These findings demonstrate for the first time that DAB2 is an αIIb-integrin-binding protein that plays a novel role in the control of platelet-fibrinogen interactions and platelet aggregation.
Original languageEnglish
Pages (from-to)4420-4430
Number of pages11
JournalJournal of Cell Science
Issue number21
Publication statusPublished - 1 Nov 2006
Externally publishedYes


  • αIIbβ3 Integrin
  • Disabled-2
  • Fibrinogen
  • Platelet aggregation
  • RGD motif

ASJC Scopus subject areas

  • Cell Biology

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