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Protease-activating receptor-4 induces full platelet spreading on a fibrinogen matrix: involvement of ERK2 and p38 and Ca2+ mobilization.
J Biol Chem. 2007 Feb 23; 282(8):5478-87.JB

Abstract

Although the involvement of protease-activating receptor PAR1 and PAR4 is well established in platelet aggregation, their role in platelet adhesion and spreading has yet to be characterized. We investigated platelet adhesion and spreading on a fibrinogen matrix after PAR1 and PAR4 stimulation in correlation with the activation of two MAPKs, ERK2 and p38. Of the two PAR-activating peptides (PAR-APs), PAR1-AP and PAR4-AP, which both induce adhesion, only PAR4-AP induced full platelet spreading. Although both PAR1-AP and PAR4-AP induced ADP secretion, which is required for platelet spreading, only PAR4-AP induced sustained Ca(2+) mobilization. In these conditions of PAR4 induction, ERK2 and p38 activation were involved in platelet spreading but not in platelet adhesion. p38 phosphorylation was dependent on ADP signaling through P2Y12, its receptor. ERK2 phosphorylation was triggered through integrin alphaIIbbeta3 outside-in signaling and was dependent on the Rho pathway. ERK2 and p38 activation induced phosphorylation of the myosin light chain and actin polymerization, respectively, necessary for cytoskeleton reorganization. These findings provide the first evidence that thrombin requires PAR4 for the full spreading response. ERK2 and p38 and sustained Ca(2+) mobilization, involved in PAR4-induced platelet spreading, contribute to the stabilization of platelet thrombi at sites of high thrombin production.

Authors+Show Affiliations

U689 INSERM, IFR139, Hôpital Lariboisière, 8 rue Guy Patin, 75010 Paris, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17200114

Citation

Mazharian, Alexandra, et al. "Protease-activating Receptor-4 Induces Full Platelet Spreading On a Fibrinogen Matrix: Involvement of ERK2 and P38 and Ca2+ Mobilization." The Journal of Biological Chemistry, vol. 282, no. 8, 2007, pp. 5478-87.
Mazharian A, Roger S, Berrou E, et al. Protease-activating receptor-4 induces full platelet spreading on a fibrinogen matrix: involvement of ERK2 and p38 and Ca2+ mobilization. J Biol Chem. 2007;282(8):5478-87.
Mazharian, A., Roger, S., Berrou, E., Adam, F., Kauskot, A., Nurden, P., Jandrot-Perrus, M., & Bryckaert, M. (2007). Protease-activating receptor-4 induces full platelet spreading on a fibrinogen matrix: involvement of ERK2 and p38 and Ca2+ mobilization. The Journal of Biological Chemistry, 282(8), 5478-87.
Mazharian A, et al. Protease-activating Receptor-4 Induces Full Platelet Spreading On a Fibrinogen Matrix: Involvement of ERK2 and P38 and Ca2+ Mobilization. J Biol Chem. 2007 Feb 23;282(8):5478-87. PubMed PMID: 17200114.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protease-activating receptor-4 induces full platelet spreading on a fibrinogen matrix: involvement of ERK2 and p38 and Ca2+ mobilization. AU - Mazharian,Alexandra, AU - Roger,Séverine, AU - Berrou,Eliane, AU - Adam,Frédéric, AU - Kauskot,Alexandre, AU - Nurden,Paquita, AU - Jandrot-Perrus,Martine, AU - Bryckaert,Marijke, Y1 - 2007/01/02/ PY - 2007/1/4/pubmed PY - 2007/4/18/medline PY - 2007/1/4/entrez SP - 5478 EP - 87 JF - The Journal of biological chemistry JO - J Biol Chem VL - 282 IS - 8 N2 - Although the involvement of protease-activating receptor PAR1 and PAR4 is well established in platelet aggregation, their role in platelet adhesion and spreading has yet to be characterized. We investigated platelet adhesion and spreading on a fibrinogen matrix after PAR1 and PAR4 stimulation in correlation with the activation of two MAPKs, ERK2 and p38. Of the two PAR-activating peptides (PAR-APs), PAR1-AP and PAR4-AP, which both induce adhesion, only PAR4-AP induced full platelet spreading. Although both PAR1-AP and PAR4-AP induced ADP secretion, which is required for platelet spreading, only PAR4-AP induced sustained Ca(2+) mobilization. In these conditions of PAR4 induction, ERK2 and p38 activation were involved in platelet spreading but not in platelet adhesion. p38 phosphorylation was dependent on ADP signaling through P2Y12, its receptor. ERK2 phosphorylation was triggered through integrin alphaIIbbeta3 outside-in signaling and was dependent on the Rho pathway. ERK2 and p38 activation induced phosphorylation of the myosin light chain and actin polymerization, respectively, necessary for cytoskeleton reorganization. These findings provide the first evidence that thrombin requires PAR4 for the full spreading response. ERK2 and p38 and sustained Ca(2+) mobilization, involved in PAR4-induced platelet spreading, contribute to the stabilization of platelet thrombi at sites of high thrombin production. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/17200114/Protease_activating_receptor_4_induces_full_platelet_spreading_on_a_fibrinogen_matrix:_involvement_of_ERK2_and_p38_and_Ca2+_mobilization_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0021-9258(20)68841-X DB - PRIME DP - Unbound Medicine ER -