Human spleen tyrosine kinase p72Syk associates with the Src-family kinase p53/56Lyn and a 120-kDa phosphoprotein.
Human spleen tyrosine kinase p72Syk associates with the Src-family kinase p53/56Lyn and a 120-kDa phosphoprotein.
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DOI：
10.1073/pnas.92.2.359
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发表时间：
1995-01
影响因子：
11.1
通讯作者：
Svetlana P. Sidorenko;Che-Leung Law;K. Chandran;Edward A. Clark
中科院分区：
文献类型：
--
作者：
Svetlana P. Sidorenko;Che-Leung Law;K. Chandran;Edward A. Clark
72-kDa 脾酪氨酸激酶 (Syk) 和 Src 家族激酶 p53/56Lyn (Lyn) 通过 B 细胞抗原受体复合物参与信号传导。在这里，我们证明来自人类 B 淋巴细胞的 Syk 和 Lyn 可以直接相互作用。 Syk 和 Lyn 从成熟和活化的 B 细胞系中进行免疫共沉淀，凝胶纯化的 Syk 和 Lyn 在体外重新结合，证明了它们的直接相互作用。这种 Syk-Lyn 相互作用可能取决于 B 细胞分化的阶段，因为在前 B 细胞系和骨髓瘤细胞系中未检测到 Syk-Lyn 关联，并且来自未成熟 B 细胞系的 Syk 在体外未与 Lyn 重新关联。丝氨酸/苏氨酸激酶活性也与 Syk 相关。细胞表面 IgM 的交联导致酪氨酸和丝氨酸/苏氨酸蛋白激酶活性的快速激活，从而导致与 Syk 共沉淀的蛋白质体外磷酸化，特别是大小为 120 kDa 的丝氨酸/苏氨酸磷酸化蛋白质 (pp120)。多种磷蛋白（包括 72 kDa 中的一种和 120 kDa 中的一种）与磷脂酶 C-gamma 1 (PLC gamma 1) 共沉淀。顺序免疫沉淀将与 PLC gamma 1 相关的 72 kDa 蛋白鉴定为 Syk。与 PLC gamma 1 共沉淀的 120-kDa 丝氨酸/苏氨酸磷酸化蛋白在几个标准上与 Syk 相关 pp120 相似。因此，pp120 可能充当 Syk 和 PLC gamma 1 之间的纽带，将 B 细胞抗原受体与磷脂酰肌醇途径偶联。
The 72-kDa spleen tyrosine kinase (Syk) and Src-family kinase p53/56Lyn (Lyn) contribute to signaling via the B-cell antigen receptor complex. Here we show that Syk and Lyn from human B lymphocytes can interact directly. Syk and Lyn coimmunoprecipitated from mature and activated B-cell lines, and gel-purified Syk and Lyn reassociated in vitro, demonstrating their direct interaction. This Syk-Lyn interaction may be dependent on the stage of B-cell differentiation, since Syk-Lyn associations were not detected in pre-B and myeloma cell lines and Syk from an immature B-cell line did not reassociate with Lyn in vitro. Serine/threonine kinase activity was also associated with Syk. Crosslinking of cell surface IgM led to rapid activation of both tyrosine and serine/threonine protein kinase activities that resulted in phosphorylation in vitro of proteins coprecipitating with Syk--in particular, a serine/threonine phosphorylated protein 120 kDa in size (pp120). Several phosphoproteins, including one of 72 kDa and one of 120 kDa, coprecipitated with phospholipase C-gamma 1 (PLC gamma 1). Sequential immunoprecipitation identified the 72-kDa protein associated with PLC gamma 1 as Syk. The 120-kDa serine/threonine phosphorylated protein that coprecipitated with PLC gamma 1 resembled the Syk-associated pp120 by several criteria. Thus, pp120 may serve as a link between Syk and PLC gamma 1, coupling the B-cell antigen receptor to the phosphatidylinositol pathway.