Prigent S A, Pillay T S, Ravichandran K S, Gullick W J
University of California, San Diego Cancer Center, La Jolla 92093-0684, USA.
J Biol Chem. 1995 Sep 22;270(38):22097-100. doi: 10.1074/jbc.270.38.22097.
Shc is an SH2-containing adapter protein that binds to and is phosphorylated by a large number of growth factor receptors. Phosphorylated Shc is able to interact with the Grb2-Sos complex which is responsible for mediating nucleotide exchange on Ras. We have shown previously that binding of Shc to the epidermal growth factor (EGF)-like receptor, c-ErbB-3, is through an NPXY motif (Prigent, S. A., and Gullick, W. J. (1994) EMBO J. 13, 2831-2841) shared by middle T antigen, TrkA, and EGF receptor. It has recently been reported that a region distinct from the SH2 domain is able to bind to tyrosine-phosphorylated proteins. In this paper we have used fusion proteins of various Shc domains to show that it is the N-terminal domain of Shc that is primarily responsible for binding EGF receptor and c-ErbB-3. Furthermore, by competition studies with synthetic phosphopeptides we have shown that this N-terminal domain binds to the previously identified NPXY motif.
Shc是一种含SH2结构域的接头蛋白，可与大量生长因子受体结合并被其磷酸化。磷酸化的Shc能够与Grb2 - Sos复合物相互作用，该复合物负责介导Ras上的核苷酸交换。我们之前已经表明，Shc与表皮生长因子（EGF）样受体c - ErbB - 3的结合是通过中间T抗原、TrkA和EGF受体共有的NPXY基序（Prigent, S. A., and Gullick, W. J. (1994) EMBO J. 13, 2831 - 2841）。最近有报道称，一个与SH2结构域不同的区域能够结合酪氨酸磷酸化蛋白。在本文中，我们使用了各种Shc结构域的融合蛋白来表明，Shc的N末端结构域主要负责结合EGF受体和c - ErbB - 3。此外，通过与合成磷酸肽的竞争研究，我们表明该N末端结构域与先前鉴定的NPXY基序结合。
