Sanjay A, Horne W C, Baron R
Departments of Orthopaedics and Cell Biology and the Yale Cancer Center, Yale University School of Medicine, New Haven, CT 06520-8044, USA.
Sci STKE. 2001 Nov 27;2001(110):pe40. doi: 10.1126/stke.2001.110.pe40.
The Cbl proteins compose a family of ubiquitin ligases that play a central role in the down-regulation of signaling cascades involving receptor and nonreceptor tyrosine kinases. Analysis of the activity of these proteins suggests that they can regulate the signaling process through ubiquitination of the plasma membrane receptors and various downstream signaling components, including the Cbl proteins themselves. Structural analysis of the Cbl proteins shows that, in many instances, they interact with phosphorylated tyrosine residues on their targets. Furthermore, phosphorylation of specific tyrosine residues on the Cbl proteins may provide an additional level of control on the ubiquitinating activity of these proteins.
Cbl蛋白构成了一个泛素连接酶家族，在涉及受体和非受体酪氨酸激酶的信号级联下调中起核心作用。对这些蛋白活性的分析表明，它们可以通过对质膜受体和各种下游信号成分（包括Cbl蛋白自身）进行泛素化来调节信号传导过程。Cbl蛋白的结构分析表明，在许多情况下，它们与靶标上的磷酸化酪氨酸残基相互作用。此外，Cbl蛋白上特定酪氨酸残基的磷酸化可能为这些蛋白的泛素化活性提供额外的控制水平。
