Two regions of the human platelet F11-receptor (F11R) are critical for platelet aggregation, potentiation and adhesion

Anna Babinska, Mamdouh H. Kedees, Humra Athar, Tomasz Sobocki, Malgorzata B. Sobocka, Tahir Ahmed, Yigal H. Ehrlich, M. Mahmood Hussain, Elizabeth Kornecki

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

The F11 receptor (F11R) was first identified on the surface of human platelets as a target for a stimulatory monoclonal antibody (M.Ab.F11) that induces secretion, followed by exposure of fibrinogen receptors and aggregation. Cloning of the gene of F11R has revealed that this protein is a cell adhesion molecule (CAM), a member of the Ig superfamily and an orthology of the murine protein called junctional adhesion molecule (JAM). The present study has identified two domains through which M.Ab.F11 triggers a platelet response culminating with aggregation. M.Ab.F11-mediated platelet adhesion, and the potentiation of collagen and ADP-induced platelet aggregation by M.Ab.F11, were found to involve the same two domains. A F11R recombinant protein (sF11R) completely inhibited platelet aggregation, adhesion and potentiation induced by M.Ab.F11, indicative that the active conformation of the external domain of F11R is present in the soluble, secreted recombinant protein. Furthermore, a specific peptide containing the sequence of the N-terminal amino acids S-1 to C-23 of F11R, and a peptide with the sequence of K-70 to C-82 in the 1st immunoglobulin-like (Ig) fold of F11R, both inhibited M.Ab.F11-induced aggregation, adhesion and potentiation of the aggregation of human platelets. Modeling of the 3D structure of the extracellular domain of the human platelet F11R suggests that these two regions form an active site within the conformation of this CAM. The sequence of these functional domains of F11R (in the N-terminus and 1st Ig-fold) provide the basis for new drug development in the treatment of certain types of thrombocytopenia and inflammatory thrombosis.

Original languageEnglish
Pages (from-to)712-721
Number of pages10
JournalThrombosis and Haemostasis
Volume87
Issue number4
StatePublished - Apr 25 2002
Externally publishedYes

Fingerprint

Junctional Adhesion Molecule A
Platelet Aggregation
Blood Platelets
Immunoglobulins
Cell Adhesion Molecules
Recombinant Proteins
Junctional Adhesion Molecules
Receptor Aggregation
Fibrinogen Receptors
Peptides
human F11R protein
Thrombocytopenia
Adenosine Diphosphate
Organism Cloning
Catalytic Domain
Proteins
Thrombosis
Collagen
Monoclonal Antibodies
Amino Acids

Keywords

  • F11R
  • Human platelet F11 receptor
  • JAM
  • Junctional adhesion molecule

ASJC Scopus subject areas

  • Hematology

Cite this

Babinska, A., Kedees, M. H., Athar, H., Sobocki, T., Sobocka, M. B., Ahmed, T., ... Kornecki, E. (2002). Two regions of the human platelet F11-receptor (F11R) are critical for platelet aggregation, potentiation and adhesion. Thrombosis and Haemostasis, 87(4), 712-721.

Two regions of the human platelet F11-receptor (F11R) are critical for platelet aggregation, potentiation and adhesion. / Babinska, Anna; Kedees, Mamdouh H.; Athar, Humra; Sobocki, Tomasz; Sobocka, Malgorzata B.; Ahmed, Tahir; Ehrlich, Yigal H.; Hussain, M. Mahmood; Kornecki, Elizabeth.

In: Thrombosis and Haemostasis, Vol. 87, No. 4, 25.04.2002, p. 712-721.

Research output: Contribution to journalArticle

Babinska, A, Kedees, MH, Athar, H, Sobocki, T, Sobocka, MB, Ahmed, T, Ehrlich, YH, Hussain, MM & Kornecki, E 2002, 'Two regions of the human platelet F11-receptor (F11R) are critical for platelet aggregation, potentiation and adhesion', Thrombosis and Haemostasis, vol. 87, no. 4, pp. 712-721.
Babinska A, Kedees MH, Athar H, Sobocki T, Sobocka MB, Ahmed T et al. Two regions of the human platelet F11-receptor (F11R) are critical for platelet aggregation, potentiation and adhesion. Thrombosis and Haemostasis. 2002 Apr 25;87(4):712-721.
Babinska, Anna ; Kedees, Mamdouh H. ; Athar, Humra ; Sobocki, Tomasz ; Sobocka, Malgorzata B. ; Ahmed, Tahir ; Ehrlich, Yigal H. ; Hussain, M. Mahmood ; Kornecki, Elizabeth. / Two regions of the human platelet F11-receptor (F11R) are critical for platelet aggregation, potentiation and adhesion. In: Thrombosis and Haemostasis. 2002 ; Vol. 87, No. 4. pp. 712-721.
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abstract = "The F11 receptor (F11R) was first identified on the surface of human platelets as a target for a stimulatory monoclonal antibody (M.Ab.F11) that induces secretion, followed by exposure of fibrinogen receptors and aggregation. Cloning of the gene of F11R has revealed that this protein is a cell adhesion molecule (CAM), a member of the Ig superfamily and an orthology of the murine protein called junctional adhesion molecule (JAM). The present study has identified two domains through which M.Ab.F11 triggers a platelet response culminating with aggregation. M.Ab.F11-mediated platelet adhesion, and the potentiation of collagen and ADP-induced platelet aggregation by M.Ab.F11, were found to involve the same two domains. A F11R recombinant protein (sF11R) completely inhibited platelet aggregation, adhesion and potentiation induced by M.Ab.F11, indicative that the active conformation of the external domain of F11R is present in the soluble, secreted recombinant protein. Furthermore, a specific peptide containing the sequence of the N-terminal amino acids S-1 to C-23 of F11R, and a peptide with the sequence of K-70 to C-82 in the 1st immunoglobulin-like (Ig) fold of F11R, both inhibited M.Ab.F11-induced aggregation, adhesion and potentiation of the aggregation of human platelets. Modeling of the 3D structure of the extracellular domain of the human platelet F11R suggests that these two regions form an active site within the conformation of this CAM. The sequence of these functional domains of F11R (in the N-terminus and 1st Ig-fold) provide the basis for new drug development in the treatment of certain types of thrombocytopenia and inflammatory thrombosis.",
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AU - Sobocki, Tomasz

AU - Sobocka, Malgorzata B.

AU - Ahmed, Tahir

AU - Ehrlich, Yigal H.

AU - Hussain, M. Mahmood

AU - Kornecki, Elizabeth

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