Hunter T, Lindberg R A, Middlemas D S, Tracy S, van der Geer P
Molecular Biology and Virology Laboratory, Salk Institute, San Diego, California 92186.
Cold Spring Harb Symp Quant Biol. 1992;57:25-41. doi: 10.1101/sqb.1992.057.01.005.
It is clear that the number of receptor PTKs and PTPs encoded by a typical vertebrate genome is rather large. Although the signal pathways activated by the receptor PTKs may in many cases be common, specificity is provided by the ligand-binding domain and the availability of ligand. In addition, the precise spectrum of substrates that bind to and are phosphorylated by each receptor PTK can differ based on the number and nature of the autophosphorylation sites and on the repertoire of SH2-containing proteins and other substrates expressed in each cell type. It is also clear that receptor PTKs can activate multiple independent signaling pathways and that the output of these pathways can be integrated to provide a specific cellular response. The role of receptor PTPs in such integrated signaling networks is not yet obvious. In some cases, they may activate nonreceptor PTKs, whereas in other cases, they may counteract the effects of activated receptor and nonreceptor PTKs by dephosphorylating the PTKs themselves or their substrates. We know very little about the substrate specificity of PTPs, but in part this must be dictated by their subcellular location. It is possible that there are specific pairs of receptor PTKs and PTPs, which act in concert at the cell surface to activate and down-regulate specific signal pathways. Progress in understanding the function of receptor PTPs will depend on identifying ligands for receptor PTPs and then determining how ligand binding influences their activity.
显然，典型脊椎动物基因组所编码的受体蛋白酪氨酸激酶（PTK）和蛋白酪氨酸磷酸酶（PTP）数量相当庞大。尽管受体PTK激活的信号通路在许多情况下可能是常见的，但配体结合结构域和配体的可获得性提供了特异性。此外，基于自身磷酸化位点的数量和性质以及每种细胞类型中表达的含SH2结构域蛋白和其他底物的全部组成，与每个受体PTK结合并被其磷酸化的底物的精确范围可能会有所不同。同样明显的是，受体PTK可以激活多个独立的信号通路，并且这些通路的输出可以整合以提供特定的细胞反应。受体PTP在这种整合信号网络中的作用尚不明确。在某些情况下，它们可能激活非受体PTK，而在其他情况下，它们可能通过使PTK自身或其底物去磷酸化来抵消激活的受体和非受体PTK的作用。我们对PTP的底物特异性了解甚少，但部分原因肯定是由它们的亚细胞定位决定的。可能存在特定的受体PTK和PTP对，它们在细胞表面协同作用以激活和下调特定的信号通路。了解受体PTP功能的进展将取决于鉴定受体PTP的配体，然后确定配体结合如何影响它们的活性。
