C-terminal SRC kinase controls acute inflammation and granulocyte adhesion

Immunity. 2004 Feb;20(2):181-91. doi: 10.1016/s1074-7613(04)00023-8.


To establish whether the widely expressed regulator of Src family kinases Csk contributes to the control of acute inflammation in vivo, we inactivated csk in granulocytes by conditional mutagenesis (Cre/loxP). Mutant mice (Csk-GEcre) developed acute multifocal inflammation in skin and lung. Animals were protected from the disease in a microbiologically controlled environment, but remained hypersensitive to LPS-induced shock. Csk-deficient granulocytes showed enhanced spontaneous and ligand-induced degranulation with hyperinduction of integrins. This hyperresponsiveness was associated with hyperadhesion and impaired migratory responses in vitro. Hyperphosphorylation of key signaling proteins such as Syk and Paxillin in mutant granulocytes further supported breakdown of the activation threshold set by Csk. By enforcing the need for ligand engagement Csk thus prevents premature granulocyte recruitment while supporting the motility of stimulated cells through negative regulation of cell adhesion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Blotting, Western
  • CSK Tyrosine-Protein Kinase
  • Cell Adhesion / immunology
  • Cell Movement
  • Cytoskeletal Proteins / metabolism
  • Enzyme Precursors / metabolism
  • Granulocytes / immunology*
  • Inflammation / immunology*
  • Intracellular Signaling Peptides and Proteins
  • Mice
  • Mice, Mutant Strains
  • Microscopy, Confocal
  • Paxillin
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Protein-Tyrosine Kinases / deficiency
  • Protein-Tyrosine Kinases / immunology*
  • Protein-Tyrosine Kinases / metabolism
  • Syk Kinase
  • src-Family Kinases


  • Cytoskeletal Proteins
  • Enzyme Precursors
  • Intracellular Signaling Peptides and Proteins
  • Paxillin
  • Phosphoproteins
  • Pxn protein, mouse
  • Protein-Tyrosine Kinases
  • CSK Tyrosine-Protein Kinase
  • Syk Kinase
  • Syk protein, mouse
  • src-Family Kinases