Saouaf S J, Mahajan S, Rowley R B, Kut S A, Fargnoli J, Burkhardt A L, Tsukada S, Witte O N, Bolen J B
Department of Molecular Biology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543.
Proc Natl Acad Sci U S A. 1994 Sep 27;91(20):9524-8. doi: 10.1073/pnas.91.20.9524.
We evaluated in WEHI 231 B cells the time-dependent responses of Lyn, Blk, Btk, Syk, and three members of the Jak family of protein tyrosine kinases following antibody-mediated surface engagement of the B-cell antigen receptor. Our results show that the enzyme activities of Lyn and Blk were stimulated within seconds of antigen receptor engagement and correlated with the initial tyrosine phosphorylation of the Ig alpha and Ig beta subunits of the B-cell antigen receptor. Btk enzyme activity was also transiently stimulated and was maximal at approximately 5 min after B-cell receptor surface binding. Syk activity gradually increased to a maximum at 10-30 min following receptor ligation and was found to parallel the association of Syk with the tyrosine phosphorylated Ig alpha and Ig beta subunits of the receptor. While the specific activities of the Jak1, Jak2, and Tyk2 protein tyrosine kinases were unaltered following B-cell receptor ligation, the abundance of Jak1 and Jak2 were increased 3- to 4-fold within 10 min of receptor engagement. These results demonstrate that multiple families of non-transmembrane protein tyrosine kinases are temporally regulated during the process of B-cell antigen receptor-initiated intracellular signal transduction.
我们在WEHI 231 B细胞中评估了B细胞抗原受体抗体介导的表面结合后，Lyn、Blk、Btk、Syk以及蛋白酪氨酸激酶Jak家族的三个成员的时间依赖性反应。我们的结果表明，Lyn和Blk的酶活性在抗原受体结合后数秒内被激活，并且与B细胞抗原受体的Igα和Igβ亚基的初始酪氨酸磷酸化相关。Btk酶活性也被短暂激活，在B细胞受体表面结合后约5分钟达到最大值。Syk活性在受体连接后10 - 30分钟逐渐增加至最大值，并且发现与Syk与受体的酪氨酸磷酸化Igα和Igβ亚基的结合平行。虽然B细胞受体连接后Jak1、Jak2和Tyk2蛋白酪氨酸激酶的比活性未改变，但Jak1和Jak2的丰度在受体结合后10分钟内增加了3至4倍。这些结果表明，在B细胞抗原受体启动的细胞内信号转导过程中，多个非跨膜蛋白酪氨酸激酶家族受到时间调控。
