Schmandt R, Liu S K, McGlade C J
Ontario Cancer Institute, University of Toronto, Canada.
Oncogene. 1999 Mar 11;18(10):1867-79. doi: 10.1038/sj.onc.1202507.
Shc adaptor proteins play a role in linking activated cell surface receptors to the Ras signaling pathway in response to receptor mediated tyrosine kinase activation. While the function of Shc in the activation of the Ras pathway via binding to Grb2 has been well characterized, it is becoming increasingly apparent that Shc participates in additional signaling pathways through interactions with other cytoplasmic proteins. Using the yeast two-hybrid system, we have identified a unique Shc binding protein designated PAL (Protein expressed in Activated Lymphocytes) with no similarity to other known proteins. mPAL binds specifically to the Shc SH2 domain and unlike previously described Shc SH2 domain-protein interactions, the association of mPAL and Shc is phosphotyrosine-independent. Both mPAL RNA and protein expression are restricted to tissues containing actively dividing cells and proliferating cells in culture. mPAL expression is induced upon growth factor stimulation and is down-regulated upon growth inhibition. This pattern, and timing of mPAL expression and its association with the Shc adaptor molecule suggests a role for this protein in signaling pathways governing cell cycle progression.
Shc衔接蛋白在响应受体介导的酪氨酸激酶激活时，参与将活化的细胞表面受体与Ras信号通路相连接。虽然Shc通过与Grb2结合在激活Ras通路中的功能已得到充分表征，但越来越明显的是，Shc通过与其他细胞质蛋白相互作用参与额外的信号通路。利用酵母双杂交系统，我们鉴定出一种独特的Shc结合蛋白，命名为PAL（活化淋巴细胞中表达的蛋白），它与其他已知蛋白没有相似性。mPAL特异性结合Shc的SH2结构域，与先前描述的Shc SH2结构域 - 蛋白相互作用不同，mPAL与Shc的结合不依赖于磷酸酪氨酸。mPAL的RNA和蛋白表达均局限于含有活跃分裂细胞和培养中增殖细胞的组织。mPAL的表达在生长因子刺激时被诱导，在生长抑制时被下调。mPAL表达的这种模式、时间及其与Shc衔接分子的关联表明该蛋白在调控细胞周期进程的信号通路中发挥作用。
