Cell and Molecular Biology, Toronto General Research Institute, Toronto, Ontario, Canada.
Exp Hematol. 2012 Dec;40(12):1055-9. doi: 10.1016/j.exphem.2012.08.007. Epub 2012 Sep 5.
SHP-1, encoded by the PTPN6 gene, is a protein tyrosine phosphatase with two src-homology-2 (SH2) domains that is implicated as providing suppression of hematopoietic malignancies. A number of reports have shown protein-protein interactions between SHP-1 SH2 domains and tyrosine-phosphorylated proteins. However, despite its having three proline-rich, potential SH3-binding motifs, no reports of protein-protein interactions through src-homology-3 (SH3)-binding domains with SHP-1 have been described. Herein we show that the SH3 domain-containing CT10 regulator of kinase-like (CrkL) adaptor protein associates with SHP-1. We also provide results that suggest this association is due to CrkL binding to PxxP domains located at amino acid residues 158-161 within the SHP-1 C-terminal SH2 domain, and amino acid residues 363-366 within its phosphatase domain. This study is the first to identify and define an interaction between SHP-1 and an SH3 domain-containing protein. Our findings provide an alternative way that SHP-1 can be linked to potential substrates.
SHP-1 由 PTPN6 基因编码，是一种具有两个 src 同源性-2（SH2）结构域的蛋白酪氨酸磷酸酶，被认为可以抑制血液系统恶性肿瘤。许多报道表明 SHP-1 SH2 结构域与酪氨酸磷酸化蛋白之间存在蛋白-蛋白相互作用。然而，尽管它具有三个富含脯氨酸的潜在 SH3 结合基序，但没有报道表明通过 src 同源性-3（SH3）结合结构域与 SHP-1 发生蛋白-蛋白相互作用。在此，我们证明了含有 SH3 结构域的激酶样（CrkL）衔接蛋白 CT10 调节剂与 SHP-1 相关联。我们还提供的结果表明，这种关联是由于 CrkL 结合到 SHP-1 C 末端 SH2 结构域中氨基酸残基 158-161 处的 PxxP 结构域，以及其磷酸酶结构域中氨基酸残基 363-366 处的 PxxP 结构域。这项研究首次鉴定并定义了 SHP-1 与含有 SH3 结构域的蛋白质之间的相互作用。我们的发现为 SHP-1 与潜在底物连接提供了另一种方式。
