A myristoylated alanine-rich C-kinase substrate (MARCKS) inhibitor peptide attenuates neutrophil outside-in β2-integrin activation and signaling

肉豆蔻酰化富含丙氨酸的 C-激酶底物 (MARCKS) 抑制剂肽可减弱中性粒细胞由外向内的 β2-整合素激活和信号传导

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作者:Haleigh Conley, Rebecca L Till, Alix K Berglund, Samuel L Jones, M Katie Sheats

Abstract

MARCKS is an actin and PIP2-binding protein that plays an essential role in neutrophil migration and adhesion; however, the molecular details regarding MARCKS function in these processes remains unclear. Neutrophil adhesion and migration also require the cell surface receptors β2-integrins. We hypothesized that MARCKS inhibition would alter neutrophil β2-integrin activation and signaling. We utilized a MARCKS-targeting peptide to inhibit MARCKS in inside-out and outside-in β2-integrin activation in neutrophils. MANS-mediated MARCKS inhibition had no significant effect on inside-out β2-integrin activation. MANS treatment significantly attenuated ICAM-1/Mn2+-stimulated static adhesion, cell spreading and β2-integrin clustering, suggesting a role for MARCKS function in outside-in β2-integrin activation. Additional work is needed to better understand the molecular mechanisms of MARCKS role in outside-in β2-integrin activation and signaling.

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