A role for the actin-bundling protein L-plastin in the regulation of leukocyte integrin function.
Regulation of leukocyte integrin avidity is a crucial aspect of inflammation and immunity. The actin cytoskeleton has an important role in the regulation of integrin function, but the cytoskeletal proteins involved are largely unknown. Because inflammatory stimuli that activate integrin-mediated adhesion in human polymorphonuclear neutrophils (PMN) and monocytes cause phosphorylation of the actin-bundling protein L-plastin, we tested whether L-plastin phosphorylation was involved in integrin activation. L-plastin-derived peptides that included the phosphorylation site (Ser-5) rapidly induced leukocyte integrin-mediated adhesion when introduced into the cytosol of freshly isolated primary human PMN and monocytes. Substitution of Ala for Ser-5 abolished the ability of the peptide to induce adhesion. Peptide-induced adhesion was sensitive to pharmacologic inhibition of phosphoinositol 3-kinase and protein kinase C, but adhesion induced by a peptide containing a phosphoserine at position 5 was insensitive to inhibition. These data establish a novel role for L-plastin in the regulation of leukocyte adhesion and suggest that many signaling events implicated in integrin regulation act via induction of L-plastin phosphorylation.
Division of Infectious Diseases, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
S L
SL
Jones
J
J
Wang
C W
CW
Turck
E J
EJ
Brown
D000595:Amino Acid Sequence; D002448:Cell Adhesion; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction
D016023:Integrins; D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; D010750:Phosphoproteins; C026742:plastin; D012694:Serine; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C