Activation of PKC induces leukocyte adhesion by the dephosphorylation of ERM

• Published in: Biochemical and biophysical research communications Vol. 523; no. 1; pp. 177 - 182
• Main Authors: Tachibana, Kouichi, Ohnishi, Hiroe, Ali Haghparast, Seyed Mohammad, Kihara, Takanori, Miyake, Jun
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 26.02.2020
• Subjects: Cell adhesion; Dephosphorylation; ERM; Leukocyte; PKC; PLC; ERM; Ab; Leukocyte; PMA; PLC; AFM; PtdIns(4,5)P2; SDF-1; PKC; Dephosphorylation; GST-CS1; IP3; BAM; Cell adhesion; FERM
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2019.12.044

Although circulating leukocytes are non-adherent cells, they also undergo adhesion in response to external stimuli. To elucidate this switch mechanism, we investigated PMA-induced cell adhesion in myelomonocytic KG-1 cells. PMA induced microvillius collapse, decrease of cell surface rigidity and exclusion of sialomucin from adhesion sites. All these adhesion-contributing events are linked to dephosphorylation of Ezrin/Radixin/Moesin (ERM) proteins. Indeed, PMA-treatment induced quick decrease of phosphorylated ERM proteins, while expression of Moesin-T558D, a phospho-mimetic mutant, inhibited PMA-induced cell adhesion. PMA-induced cell adhesion and ERM-dephophorylation were inhibited by PKC inhibitors or by a phosphatase inhibitor, indicating the involvement of PKC and protein phophatase in these processes. In peripheral T lymphocytes, ERM-dephosphorylation by adhesion-inducing stimuli was inhibited by a PKC inhibitor. Combined, these findings strongly suggest that external stimuli induce ERM-dephosphorylation via the activation of PKC in leukocytes and that ERM-dephosphorylation leads to leukocytes’ adhesion. •PMA induced cell adhesion, microvilli collapse and decreased rigidity in KG-1 cells.•PMA also induced Ezrin/Radixin/Moesin (ERM)-dephosphorylation in KG-1 cells.•Expression of Moesin phospho-mimetic mutant inhibited PMA-induced KG-1 cell adhesion.•PKC inhibitors inhibited cell adhesion and ERM-dephosphorylation in KG-1 cells.•A PKC inhibitor inhibited stimuli-induced ERM-dephosphorylation in T lymphocytes.