Spuches A M, Argiros H J, Lee K H, Haas L Lowell, Pero S C, Krag D N, Roller P P, Wilcox D E, Lyons B A
Department of Chemistry, Dartmouth College, Hanover, NH 03755, USA.
J Mol Recognit. 2007 Jul-Aug;20(4):245-52. doi: 10.1002/jmr.834.
Grb7 is a member of the Grb7 family of proteins, which also includes Grb10 and Grb14. All three proteins have been found to be overexpressed in certain cancers and cancer cell lines. In particular, Grb7 (along with the receptor tyrosine kinase erbB2) is overexpressed in 20-30% of breast cancers. In general, growth factor receptor bound (Grb) proteins bind to activated membrane-bound receptor tyrosine kinases (RTKs; e.g., the epidermal growth factor receptor, EGFR) through their Src homology 2 (SH2) domains. In particular, Grb7 binds to erbB2 (a.k.a. EGFR2) and may be involved in cell signaling pathways that promote the formation of metastases and inflammatory responses. In previous studies, we reported the solution structure and the backbone relaxation behavior of the Grb7-SH2/erbB2 peptide complex. In this study, isothermal titration calorimetry studies have been completed by measuring the thermodynamic binding parameters of several phosphorylated and non-phosphorylated peptides representative of natural Grb7 receptor ligands as well as ligands developed through combinatorial peptide screening methods. The entirety of these calorimetric studies is interpreted in an effort to describe the specific ligand binding characteristics of the Grb7 protein.
Grb7是Grb7蛋白家族的成员，该家族还包括Grb10和Grb14。已发现这三种蛋白在某些癌症及癌细胞系中均有过表达。特别是，Grb7（连同受体酪氨酸激酶erbB2）在20%至30%的乳腺癌中过表达。一般来说，生长因子受体结合（Grb）蛋白通过其Src同源2（SH2）结构域与活化的膜结合受体酪氨酸激酶（RTK；例如表皮生长因子受体，EGFR）结合。具体而言，Grb7与erbB2（又称EGFR2）结合，并可能参与促进转移形成和炎症反应的细胞信号通路。在先前的研究中，我们报道了Grb7-SH2/erbB2肽复合物的溶液结构和主链弛豫行为。在本研究中，通过测量几种代表天然Grb7受体配体以及通过组合肽筛选方法开发的配体的磷酸化和非磷酸化肽的热力学结合参数，完成了等温滴定量热法研究。对这些量热研究的整体结果进行了解释，以描述Grb7蛋白的特定配体结合特性。
