Centre for Biological Signalling Studies, BIOSS, University of Freiburg, 79104 Freiburg, Germany.
Proc Natl Acad Sci U S A. 2010 Oct 26;107(43):18563-8. doi: 10.1073/pnas.1009048107. Epub 2010 Oct 12.
Upon B-cell activation, the signaling subunits Ig-α and Ig-β of the B-cell antigen receptor become phosphorylated not only on tyrosines but also on serine residues. Using a specific antibody, we show that serine 197 (S197) in the cytoplasmic tail of Ig-α is phosphorylated upon B-cell antigen receptor activation, and that this modification inhibits the signal output of the B-cell antigen receptor. Surprisingly, we found that the well-known protein tyrosine kinase Syk (spleen tyrosine kinase) phosphorylates S197 on Ig-α, thus not only activating but also inhibiting signaling from the B-cell antigen receptor. This finding identifies Syk as a dual-specificity kinase and establishes a previously unexplored paradigm for the self-regulation of biological signaling processes.
在 B 细胞激活后，B 细胞抗原受体的信号亚基 Ig-α 和 Ig-β 不仅在酪氨酸上被磷酸化，而且在丝氨酸残基上也被磷酸化。使用特异性抗体，我们表明 B 细胞抗原受体激活后 Ig-α 胞质尾部的丝氨酸 197（S197）被磷酸化，并且这种修饰抑制 B 细胞抗原受体的信号输出。令人惊讶的是，我们发现众所周知的蛋白酪氨酸激酶 Syk（脾酪氨酸激酶）磷酸化 Ig-α 上的 S197，从而不仅激活而且抑制 B 细胞抗原受体的信号转导。这一发现将 Syk 鉴定为双特异性激酶，并为生物信号转导过程的自我调节建立了一个以前未知的范例。
