Activation of Lyn is a common element of the stimulation of human neutrophils by soluble and particulate agonists.
The functional responsiveness of human neutrophils is known to be initiated and modulated by protein tyrosine phosphorylation. The regulation of the levels of tyrosine phosphorylation is most likely the result of the coordinated actions of tyrosine kinases and phosphatases, which have so far been only very partially characterized. In the present study, we present evidence demonstrating that the stimulation of neutrophils by a variety of agonists (soluble as well as particulate) leads to the activation of the src-related tyrosine kinase lyn. The stimulation of tyrosine kinase activity of lyn was detected using an immune kinase assay as well as an in situ labeling technique. Phosphoaminoacid analysis of lyn indicated that the autophosphorylation of the kinase was exclusively on tyrosine residues. The time course of the activation of lyn is consistent with its playing a role in the early tyrosine phosphorylation responses of neutrophils. The ability of agonists with widely varying functional end responses to stimulate the activity of lyn indicates that this event plays a key and central role in the control of the activation of human neutrophils.
Gaudry
M
M
Laboratoire d'Immunologie et d'Hématologie, INSERM U294, Paris, France.
Gilbert
C
C
Barabé
F
F
Poubelle
P E
PE
Naccache
P H
PH
D000328:Adult; D002131:Calcium Pyrophosphate / Q000494:pharmacology; D018925:Chemokines / Q000494:pharmacology; D002630:Chemotactic Factors / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D018375:Neutrophil Activation / Q000187:drug effects*; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology; D010766:Phosphorylation / Q000187:drug effects; D019000:Phosphotyrosine / Q000032:analysis; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D013211:Staphylococcus aureus; D014527:Uric Acid / Q000494:pharmacology; D015054:Zymosan / Q000494:pharmacology; D019061:src-Family Kinases / Q000096:biosynthesis* / Q000235:genetics
D018925:Chemokines; D002630:Chemotactic Factors; D007074:Immunoglobulin G; D011994:Recombinant Proteins; D019000:Phosphotyrosine; D014527:Uric Acid; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D015054:Zymosan; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D017027:Protein Tyrosine Phosphatases; D002131:Calcium Pyrophosphate