Translocation of the FGR protein-tyrosine kinase as a consequence of neutrophil activation.
Recent studies of the FGR protooncogene have shown that expression of its mRNA is limited to mature peripheral blood granulocytes, monocytes, and tissue macrophages. In the present study, we have investigated p55c-fgr expression in normal human neutrophils [polymorphonuclear leukocytes (PMN)] and have found enzymatically active p55c-fgr to be abundant in lysates of PMN and murine fibroblasts transfected with a FGR expression plasmid but not control cells. Fractionation studies revealed that neutrophil p55c-fgr was present in plasma membrane-enriched fractions as well as fractions containing secondary and tertiary granules. Little change in the distribution of p55c-fgr or FGR kinase activity was observed under conditions favoring tertiary granule release. In contrast, when secondary granule secretion was induced with the chemoattractant peptide, formyl-Met-Leu-Phe, a marked decrease in p55c-fgr and FGR kinase was observed in fractions depleted of secondary granules. Concomitantly, the relative concentration of p55c-fgr and its enzymatic activity were increased in fractions containing plasma membrane. From these findings we conclude that p55c-fgr is associated with functional secretory granules and is redistributed within normal neutrophils in response to their activation.
Gutkind
J S
JS
Laboratory of Cellular Development and Oncology, National Institute of Dental Research, Bethesda, MD 20892.
Robbins
K C
KC
D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D002478:Cells, Cultured; D003594:Cytoplasmic Granules / Q000201:enzymology; D015870:Gene Expression; D006801:Humans; D015151:Immunoblotting; D066298:In Vitro Techniques; D051379:Mice; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D011519:Proto-Oncogenes; D014162:Transfection; D019061:src-Family Kinases
D011518:Proto-Oncogene Proteins; D009240:N-Formylmethionine Leucyl-Phenylalanine; D011505:Protein-Tyrosine Kinases; C053102:proto-oncogene proteins c-fgr; D019061:src-Family Kinases