Sweeney C, Carraway K L
Department of Cell Biology, Harvard Medical School and Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, Massachusetts, MA 02215, USA.
Oncogene. 2000 Nov 20;19(49):5568-73. doi: 10.1038/sj.onc.1203913.
The four members of the ErbB family of receptor tyrosine kinases (RTKs) mediate a variety of cellular responses to epidermal growth factor (EGF)-like growth factors, and serve as a model for the generation of both diversity and specificity in RTK signaling. Previous studies indicate that receptor-receptor interactions figure prominently in signaling through ErbB receptors. In addition to a role in receptor kinase activation, ligand-induced ErbB receptor homo- and heterodimerization is thought to account for the diversity of biological responses stimulated by EGF-like growth factors. Since each receptor has the potential to couple to different complements of signaling pathways, EGF-like ligands specify cellular response by dictating which pairs of receptors become activated. More recently evidence has been uncovered for ligand discrimination by individual ErbB receptor dimers; receptors appear to realize which ligand is binding and differentially respond through autophosphorylation site usage. These observations indicate that ligand stimulation of RTKs is not generic, and point to another layer in the ErbB signal diversification mechanism. The mechanistic implications of ligand discrimination are discussed.
受体酪氨酸激酶（RTK）的表皮生长因子受体（ErbB）家族的四名成员介导了细胞对表皮生长因子（EGF）样生长因子的多种反应，并作为RTK信号传导中多样性和特异性产生的模型。先前的研究表明，受体-受体相互作用在通过ErbB受体的信号传导中起重要作用。除了在受体激酶激活中的作用外，配体诱导的ErbB受体同源和异源二聚化被认为是EGF样生长因子刺激的生物学反应多样性的原因。由于每个受体都有可能与不同的信号通路互补偶联，EGF样配体通过决定哪对受体被激活来指定细胞反应。最近，有证据表明单个ErbB受体二聚体对配体有区分作用；受体似乎能够识别结合的是哪种配体，并通过自身磷酸化位点的使用产生不同的反应。这些观察结果表明，RTK的配体刺激并非普遍存在，并指出了ErbB信号多样化机制中的另一层。本文讨论了配体区分的机制意义。
