Ota Y, Samelson L E
Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-5430, USA.
Science. 1997 Apr 18;276(5311):418-20. doi: 10.1126/science.276.5311.418.
Engagement of antigen and immunoglobulin receptors on hematopoietic cells is directly coupled to activation of nonreceptor protein tyrosine kinases (PTKs) that then phosphorylate critical intracellular substrates. In mast cells stimulated through the FcvarepsilonRI receptor, activation of several PTKs including Syk leads to degranulation and release of such mediators of the allergic response as histamine and serotonin. Regulation of Syk function occurred through interaction with the Cbl protein, itself a PTK substrate in this system. Overexpression of Cbl led to inhibition of Syk and suppression of serotonin release from mast cells, demonstrating its ability to inhibit a nonreceptor tyrosine kinase. Complex adaptor proteins such as Cbl can directly regulate the functions of the proteins they bind.
造血细胞上抗原和免疫球蛋白受体的结合直接与非受体蛋白酪氨酸激酶（PTK）的激活相关联，这些激酶随后会磷酸化关键的细胞内底物。在通过FcεRI受体刺激的肥大细胞中，包括Syk在内的几种PTK的激活会导致脱颗粒以及组胺和5-羟色胺等过敏反应介质的释放。Syk功能的调节是通过与Cbl蛋白相互作用实现的，Cbl蛋白本身就是该系统中的一种PTK底物。Cbl的过表达导致Syk受到抑制，肥大细胞中5-羟色胺释放受到抑制，这表明它具有抑制非受体酪氨酸激酶的能力。像Cbl这样的复杂衔接蛋白可以直接调节它们所结合蛋白的功能。
