Yes-associated protein (YAP65) is a proline-rich phosphoprotein that binds to the SH3 domain of the Yes proto-oncogene product.
Yes-associated protein (YAP65) is a proline-rich phosphoprotein that binds to the SH3 domain of the Yes proto-oncogene product.
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作者：
M. Sudol
Yes属于Src蛋白酪氨酸激酶家族。为了了解其信号传导的分子方面，我们决定分离与Yes分子的调节区域结合的蛋白质。通过对Yes蛋白的氨基末端结构域产生抗独特型抗体，我们已经鉴定、表征并克隆了一种新蛋白的cDNA，该蛋白结合Yes原癌基因产物的Src同源结构域3（SH3）。该蛋白质的分子量为65千道尔顿（kDa），其在体内在丝氨酸上被磷酸化，并且特别富含脯氨酸。我们将其命名为YAP 65，即65 kDa的Yes相关蛋白。在YAP 65序列中，我们鉴定了一个基序PVKQPPPLAP，与结合Abl激酶SH3结构域的蛋白质中发现的基序相似。与合成肽的竞争试验表明，参与预测的脯氨酸丰富的序列之间的YAP 65和Yes激酶的结合。YAP 65蛋白还显示与包含SH3结构域的其他信号分子结合，包括Nck，Crk和Src。在较低的化学计量比，YAP 65也被证明结合的SH3结构域的Abl和鸟苷三磷酸酶激活蛋白（GAP）。YAP65的进一步表征应该阐明Yes信号通路，并且还可以确定蛋白质酪氨酸和丝氨酸激酶之间的新联系。
Yes belongs to the Src family of protein-tyrosine kinases. In order to understand molecular aspects of its signaling, we decided to isolate proteins that bind to the modulatory region of the Yes molecule. By generating anti-idiotypic antibodies against the aminoterminal domain of the Yes protein, we have identified, characterized and cloned a cDNA for a novel protein that binds to the Src homology domain 3 (SH3) of the Yes proto-oncogene product. The protein is of 65 kiloDalton (kDa) molecular mass, it is phosphorylated in vivo on serine and is particularly rich in proline. We named it YAP65 for Yes-Associated Protein of 65 kDa. Within the YAP65 sequence, we identified a motif, PVKQPPPLAP, similar to that found in proteins that bind to the SH3 domain of the Abl kinase. Competition assays with synthetic peptides showed the involvement of the predicted proline-rich sequence in binding between YAP65 and the Yes kinase. The YAP65 protein was also shown to bind to other signaling molecules that contain SH3 domains including Nck, Crk and Src. At lower stoichiometry, YAP65 was also shown to bind to the SH3 domains of Abl and guanosine triphosphatase activating protein (GAP). Further characterization of YAP65 should illuminate Yes signaling pathways and could also identify a novel link between protein-tyrosine and serine kinases.