Williams G T, Peaker C J, Patel K J, Neuberger M S
Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom.
Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):474-8. doi: 10.1073/pnas.91.2.474.
The B-cell antigen receptor is composed of membrane immunoglobulin sheathed by an alpha/beta heterodimer. The complex is noncovalently associated with protein kinase activity, and crosslinking of the receptor leads to capping and transmembrane signaling. Here we show that the sheath is not necessary either for this capping or for the association of membrane immunoglobulin with the detergent-insoluble cytoskeletal fraction that occurs following crosslinking. It is also not required for association of membrane immunoglobulin with a casein-kinase-like serine/threonine kinase. The sheath is essential, however, for transmembrane signaling. Provision of just the cytoplasmic domain of the beta sheath polypeptide to a mutant, unsheathed IgM molecule was sufficient to restore full signaling capability as judged by the phosphorylation of a variety of cellular proteins, including the B-cell-specific transmembrane protein CD22. This signaling was destroyed by mutating one of the tyrosines in the beta cytoplasmic domain. These results not only suggest that receptor signaling is mediated through phosphorylation of the tyrosines in the sheath's cytoplasmic domains but, together with previous work, indicate that different motifs within the sheath mediate presentation and signaling.
B细胞抗原受体由被α/β异二聚体包裹的膜免疫球蛋白组成。该复合物与蛋白激酶活性非共价结合，受体交联导致帽化和跨膜信号传导。在这里我们表明，无论是这种帽化还是交联后膜免疫球蛋白与去污剂不溶性细胞骨架部分的结合，鞘都不是必需的。膜免疫球蛋白与酪蛋白激酶样丝氨酸/苏氨酸激酶的结合也不需要鞘。然而，鞘对于跨膜信号传导是必不可少的。将β鞘多肽的细胞质结构域仅提供给突变的、无鞘的IgM分子，就足以恢复通过多种细胞蛋白（包括B细胞特异性跨膜蛋白CD22）的磷酸化判断的完全信号传导能力。通过突变β细胞质结构域中的一个酪氨酸，这种信号传导被破坏。这些结果不仅表明受体信号传导是通过鞘细胞质结构域中酪氨酸的磷酸化介导的，而且与先前的工作一起表明，鞘内的不同基序介导呈递和信号传导。
