Khurshid Rukhshan, Saleem Mahjabeen, Akhthar Muhammad Saleem
Department of Biochemistry, Fatima Jinnah Medical College, Lahore, Pakistan.
Institute of Biochemistry and Biotechnology, University of the Punjab, Lahore, Pakistan.
Acta Biochim Pol. 2014;61(4):699-703. Epub 2014 Nov 14.
The protein kinase c-erbB-2 belongs to the family of receptor tyrosine kinase and is involved in oncogenesis. The present study predicts different phosphorylation sites of HER2/c-erbB-2 which are important in preventing or developing cancer, especially breast cancer. Sequence homology showed highest homology (77%) with epidermal growth factor receptor kinase domain. According to PROSITE search result, active sites of c-erbB-2 are N-lobe (glycine rich phosphate binding loop). Catalytic loop with presumptive catalytically active of Asp108 is phosphorylated by tyrosine protein kinase. A-loop, activation loop, becomes phosphorylated and activates the substrate binding. The study strengthens our knowledge regarding HER2 signaling by the detection of uncharacterized signaling proteins, establishing phosphorylation of an activation loop and helps us to make assumptions about the role of such previously unidentified proteins. On the basis of importance of HER2 in breast cancer as well as in other diseases, this study provides fruitful information for designing new therapeutic strategies.
蛋白激酶c-erbB-2属于受体酪氨酸激酶家族，参与肿瘤发生。本研究预测了HER2/c-erbB-2的不同磷酸化位点，这些位点在预防或引发癌症尤其是乳腺癌方面具有重要意义。序列同源性显示，其与表皮生长因子受体激酶结构域的同源性最高（77%）。根据PROSITE搜索结果，c-erbB-2的活性位点是N-叶（富含甘氨酸的磷酸结合环）。具有假定催化活性的Asp108的催化环被酪氨酸蛋白激酶磷酸化。A环即激活环发生磷酸化并激活底物结合。该研究通过检测未表征的信号蛋白，证实激活环的磷酸化，加强了我们对HER2信号传导的认识，并帮助我们对这类先前未鉴定蛋白的作用进行推测。基于HER2在乳腺癌以及其他疾病中的重要性，本研究为设计新的治疗策略提供了丰富的信息。
