CD66 FAMILY MEMBERS ARE ASSOCIATED WITH TYROSINE KINASE-ACTIVITY IN HUMAN NEUTROPHILS

The granulocyte activation Ags, CD66a, CD66b, CD66c, and CD66d, are ex pressed at low levels on resting blood granulocytes, but their surface expression is up-regulated following stimulation. CD66a, in contrast to CD66b and CD66c which are anchored to the membrane via a glycosyl-p hosphatidylinositol linkage, is a transmembrane protein with a cytopla smic domain. We have previously reported that CD66a is phosphorylated in human neutrophils, largely on tyrosine, with a lower level of phosp hoserine. We have now found that CD66a undergoes a rapid increase in p hosphorylation following stimulation with FMLP, platelet-activating fa ctor, and 12-O-tetradecanoyl-phorbol-13-acetate. This increase in phos phorylation was transient, with maximal phosphorylation observed by 1 min and a return to base line by 5 min following stimulation. Protein kinase activity was detected in neutrophils associated with CD66a, CD6 6b, and CD66c. Most of the protein kinase activity associated with the se Ags was tyrosine kinase activity, with a lesser amount of threonine and serine kinase activities. Lyn and Hck accounted for much of the a ssociated tyrosine kinase activity. The data suggest that phosphorylat ion of CD66a on tyrosine by an associated tyrosine kinase may play a r ole in the function of CD66a. In addition, associated tyrosine kinase activity may play a role in signal transduction from CD66a, CD66b, and CD66c to regulate other cell functions.