Pandey P, Kharbanda S, Kufe D
Division of Cancer Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Cancer Res. 1995 Sep 15;55(18):4000-3.
The DF3/MUC1 mucin-like glycoprotein is aberrantly overexpressed in human breast carcinomas. Although the precise functional role of this protein remains unclear, the cytoplasmic tail contains potential tyrosine phosphorylation sites for binding to Src homology 2 (SH2) domains. In the present studies using human MCF-7 breast cancer cells, we show that tyrosine phosphorylated DF3 directly interacts with the SH2 domain of the adaptor protein Grb2. The findings indicate that a pYTNP site in DF3 is responsible for this interaction. The results also demonstrate that the DF3/Grb2 complex associates with the guanine nucleotide exchange protein Sos. Because Sos binds to the SH3 domains of Grb2 and, thereby, associates with Ras at the cell membrane, formation of a DF3/Grb2/Sos complex supports a role for DF3 in intracellular signaling.
DF3/MUC1粘蛋白样糖蛋白在人类乳腺癌中异常过表达。尽管该蛋白的确切功能作用尚不清楚，但其胞质尾部含有与Src同源2（SH2）结构域结合的潜在酪氨酸磷酸化位点。在使用人MCF-7乳腺癌细胞的本研究中，我们表明酪氨酸磷酸化的DF3直接与衔接蛋白Grb2的SH2结构域相互作用。这些发现表明DF3中的一个pYTNP位点负责这种相互作用。结果还证明DF3/Grb2复合物与鸟嘌呤核苷酸交换蛋白Sos相关联。由于Sos与Grb2的SH3结构域结合，从而在细胞膜处与Ras相关联，DF3/Grb2/Sos复合物的形成支持了DF3在细胞内信号传导中的作用。
