Richard S, Shaw A S, Showell H J, Connelly P A
Department of Molecular Genetics and Protein Chemistry, Pfizer Inc., Groton, CT 06340.
Biochem Biophys Res Commun. 1994 Mar 15;199(2):653-61. doi: 10.1006/bbrc.1994.1278.
Having previously shown that heat-aggregated IgG stimulates a significant increase in tyrosine phosphorylation in the human neutrophil, we next sought to determine the role of individual Fc gamma receptors in this response. Specific cross-linking of Fc gamma RII reproduced the phosphorylation observed with heat-aggregated IgG treatment and monoclonal antibodies recognizing the ligand binding domain of Fc gamma RII efficiently blocked the heat-aggregated IgG induced response. Thus engagement of Fc gamma RII alone appears sufficient to mimic the heat-aggregated IgG stimulation. Similar experiments carried out with antibodies specific for Fc gamma RIII suggested that Fc gamma RII and Fc gamma RIII may cooperate in the phosphorylation response. The activation of a tyrosine kinase by Fc gamma R engagement was demonstrated by the specific immunoprecipitation of several tyrosine phosphorylated proteins from lysates of neutrophils following treatment with aggregated IgG.
先前我们已表明，热聚集的IgG可刺激人中性粒细胞中酪氨酸磷酸化显著增加，接下来我们试图确定各个Fcγ受体在此反应中的作用。FcγRII的特异性交联重现了热聚集IgG处理时观察到的磷酸化，识别FcγRII配体结合域的单克隆抗体有效阻断了热聚集IgG诱导的反应。因此，单独FcγRII的结合似乎足以模拟热聚集IgG的刺激。用针对FcγRIII的特异性抗体进行的类似实验表明，FcγRII和FcγRIII可能在磷酸化反应中协同作用。在用聚集IgG处理后的中性粒细胞裂解物中，通过对几种酪氨酸磷酸化蛋白的特异性免疫沉淀，证明了Fcγ受体结合可激活酪氨酸激酶。
