title: PAK4 phosphorylates myosin regulatory light chain and contributes to Fcγ receptor-mediated phagocytosis.
abstract: Phagocytosis of immunoglobulin G-opsonised particles takes place via Fcγ receptor ligation, leading to uptake through an actin-dependent mechanism. Myosin regulatory light chains have previously been reported to control contractility during uptake through the Fcγ receptor. In this study, we show that p21-activated kinase 4 contributes to Fcγ receptor-mediated uptake downstream of actin cup formation by regulating phosphorylation of myosin regulatory light chain. siRNA-mediated knockdown of p21-activated kinase 4 leads to reduced myosin regulatory light chain phosphorylation at Serine 19, with a corresponding reduction in phospho-myosin regulatory right chain localised to bound immunoglobulin G-opsonised red blood cells. p21-activated kinase 4 phosphorylates myosin light chain 9 at Serine 19 in vitro and RNA interference against myosin light chain 9 implicates this isoform, but not myosin light chain 12A or 12B, in Fcγ receptor-mediated uptake. Taken together, these data indicate that p21-activated kinase 4 regulates regulatory myosin light chain phosphorylation and myosin contractility during FcγR-mediated phagocytosis.
authors: Centre for Molecular Microbiology and Infection, Division of Cell and Molecular Biology, Imperial College, London SW7 2AZ, UK. michael.bright@icr.ac.uk
authors: Michael D
authors: MD
authors: Bright
authors: Gad
authors: G
authors: Frankel
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008855:Microscopy, Electron, Scanning; D018994:Myosin Light Chains / Q000235:genetics / Q000378:metabolism*; D010587:Phagocytosis; D010766:Phosphorylation; D017452:Receptors, IgG / Q000378:metabolism*; D014162:Transfection; D054462:p21-Activated Kinases / Q000378:metabolism*
chemical_list: D018994:Myosin Light Chains; D017452:Receptors, IgG; C492065:Pak4 protein, mouse; D054462:p21-Activated Kinases