title: Integrin αIIbβ3-Dependent ERK Signaling Is Regulated by Src and Rho Kinases in Both Leu33 and Pro33 Polymorphic Isoforms.
abstract: Platelet integrin αIIbβ3 possesses a Leu/Pro polymorphism at residue 33 (Leu33/HPA-1a or Pro33/HPA-1b). The Pro33 isoform has been suggested to exhibit prothrombotic features. αIIbβ3-expressing CHO (Chinese hamster ovary) cells on immobilized fibrinogen show activation of the MAP kinase family member ERK2, with an enhanced ERK2 activity in Pro33 cells compared to Leu33 cells. In our present work, we examined how the Leu/Pro polymorphism modulates the ERK2 activation stimulated by 2 differently triggered outside-in signalings. We either treated the CHO cells with Mn2+ or allowed them to adhere to fibrinogen. Moreover, we studied which signaling cascades are involved in ERK2 activation. In contrast to immobilized fibrinogen, Mn2+ did not significantly increase ERK2 activation. However, Mn2+ had a synergistic effect on ERK2 phosphorylation when combined with immobilized fibrinogen. Pro33 cells adherent to fibrinogen exhibited a significantly greater ERK2 activity than Leu33 cells in the presence of Mn2+, which peaked after 10 min of adhesion. Our data showed that Src family and rho kinases play a crucial role in the integrin αIIbβ3-dependent outside-in signaling to ERK2.
authors.affiliation: Biomedical Engineering Department, International University, Vietnam National University, Ho Chi Minh City, Vietnam.
authors.forename: Khon C
authors.initials: KC
authors.lastname: Huynh
authors.forename: Thi-Hiep
authors.initials: TH
authors.lastname: Nguyen
authors.forename: Dinh Chuong
authors.initials: DC
authors.lastname: Pham
authors.forename: Huong T T
authors.initials: HT
authors.lastname: Nguyen
authors.forename: Toi
authors.initials: T
authors.lastname: Van Vo
authors.forename: Marianna
authors.initials: M
authors.lastname: Gyenes
authors.forename: Volker R
authors.initials: VR
authors.lastname: Stoldt
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D016466:CHO Cells; D002413:Cations, Divalent; D002448:Cell Adhesion / Q000187:drug effects; D003412:Cricetulus; D005340:Fibrinogen / Q000737:chemistry / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D020935:MAP Kinase Signaling System; D008345:Manganese / Q000494:pharmacology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics* / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D010766:Phosphorylation; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000235:genetics* / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D054460:rho-Associated Kinases / Q000235:genetics* / Q000378:metabolism; D019061:src-Family Kinases / Q000235:genetics* / Q000378:metabolism
chemical_list: D002413:Cations, Divalent; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D020033:Protein Isoforms; D011994:Recombinant Proteins; D008345:Manganese; D005340:Fibrinogen; D019061:src-Family Kinases; D054460:rho-Associated Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3