Plasma kallikrein enhances platelet aggregation response by subthreshold doses of ADP.

ABSTRACT: Human plasma kallikrein (huPK) potentiates platelet responses to subthreshold doses of ADP, although huPK itself, does not induce platelet aggregation. In the present investigation, we observe that huPK pretreatment of platelets potentiates ADP-induced platelet activation by prior proteolysis of the G-protein-coupled receptor PAR-1. The potentiation of ADP-induced platelet activation by huPK is mediated by the integrin α_IIbβ₃ through interactions with the KGD/KGE sequence motif in huPK. Integrin α_IIbβ₃ is a cofactor for huPK binding to platelets to support PAR-1 hydrolysis that contributes to activation of the ADP signaling pathway. This activation pathway leads to phosphorylation of Src, AktS⁴⁷³, ERK1/2, and p38 MAPK, and to Ca²⁺

SUBMITTER: Ottaiano TF 

PROVIDER: S-EPMC5346445 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature